| 1. |
- Deshpande, J, et al.
(författare)
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Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death.
- 1992
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Ingår i: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. - 0014-4819. ; 88:1, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutaneously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.
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| 2. |
- Johansson, C, et al.
(författare)
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Nitric oxide synthase inhibition blocks phencyclidine-induced behavioural effects on prepulse inhibition and locomotor activity in the rat.
- 1997
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Ingår i: Psychopharmacology. - 0033-3158. ; 131:2, s. 167-73
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Tidskriftsartikel (refereegranskat)abstract
- The ability of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), to block the behavioural effects of the potent psychotomimetic, phencyclidine, was tested in rats using two different behavioural models. L-NAME was found to block both phencyclidine-induced disruption of prepulse inhibition of acoustic startle and phencyclidine-induced stimulation of locomotor activity. A selective action of L-NAME on the effects of phencyclidine was indicated, since L-NAME did not alter the effects of amphetamine, another potent psychotomimetic, in these behavioural models. These observations suggest that a nitric oxide-dependent mechanism may be involved in the effects of phencyclidine in the central nervous system.
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| 3. |
- Zhang, Jianhua, 1961, et al.
(författare)
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Repeated administration of amphetamine induces sensitisation to its disruptive effect on prepulse inhibition in the rat.
- 1998
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Ingår i: Psychopharmacology. - 0033-3158. ; 135:4, s. 401-6
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Tidskriftsartikel (refereegranskat)abstract
- Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg, SC) at 3- day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment regimen induced sensitisation in the animals as evidenced by a progressive increase in the disruptive effect of AMP on prepulse inhibition. Persistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22-day-long drug- and test-free period. The development of sensitisation was blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP was dependent on dopamine (DA) D2 receptor activation. Furthermore, the development of sensitisation was blocked by adrenalectomy, which suggests that sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functions that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.
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| 4. |
- Eghbali, M, et al.
(författare)
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Hippocampal GABA(A) channel conductance increased by diazepam
- 1997
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 388:6637, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Benzodiazepines, which are widely used clinically for relief of anxiety and for sedation, are thought to enhance synaptic inhibition in the central nervous system by increasing the open probability of chloride channels activated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here we show that the benzodiazepine diazepam can also increase the conductance of GABAA channels activated by low concentrations of GABA (0.5 or 5 microM) in rat cultured hippocampal neurons. Before exposure to diazepam, chloride channels activated by GABA had conductances of 8 to 53pS. Diazepam caused a concentration-dependent and reversible increase in the conductance of these channels towards a maximum conductance of 70-80 pS and the effect was as great as 7-fold in channels of lowest initial conductance. Increasing the conductance of GABAA channels tonically activated by low ambient concentrations of GABA in the extracellular environment may be an important way in which these drugs depress excitation in the central nervous system. That any drug has such a large effect on single channel conductance has not been reported previously and has implications for models of channel structure and conductance.
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| 5. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Bicarbonate-sensitive cysteine induced elevation of extracellular aspartate and glutamate in rat hippocampus in vitro
- 1997
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Ingår i: Neurochemistry International. - 0197-0186. ; 30:3, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- The effect of different concentrations of cysteine (0.125, 0.25, 0.5 and 1 mM) on the net efflux of endogenous amino acids was studied by the incubation of rat hippocampal slices. Addition of cysteine (1 mM) in bicarbonate containing low K+ medium (5 min) selectively increased the basal net efflux of glutamate and aspartate by 370% and 396%, respectively. High K+ media (50 mM) containing cysteine (1 mM) evoked the net efflux of glutamate and aspartate by 1454% and 1019%, respectively. The corresponding effects in control slices without cysteine were 669% and 404%, respectively. No changes were observed on the concentrations of GABA, glutamine and taurine. The cysteine oxidation products, cysteine sulfinate (0.5 μM) and cystine (0.25 mM) were without effects. The effect of cysteine (0.5 mM) was dramatically reduced in media with no added bicarbonate/CO2. Thus, cysteine in a bicarbonate-sensitive manner selectively increases the extracellular concentration of excitotoxic amino acids in adult rat brain in vitro, possibly by interfering with the carrier-mediated glutamate uptake/ release
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| 6. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Bicarbonate-sensitive cysteine induced elevation of extracellular aspartate and glutamate in rat hippocampus in vitro
- 1997
-
Ingår i: Neurochemistry International. - 0197-0186. ; 30:3, s. 253-259
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of different concentrations of cysteine (0.125, 0.25, 0.5 and 1 mM) on the net efflux of endogenous amino acids was studied by the incubation of rat hippocampal slices. Addition of cysteine (1 mM) in bicarbonate containing low K+ medium (5 min) selectively increased the basal net efflux of glutamate and aspartate by 370% and 396%, respectively. High K+ media (50 mM) containing cysteine (1 mM) evoked the net efflux of glutamate and aspartate by 1 454% and 1 019%, respectively. The corresponding effects in control slices without cysteine were 669% and 404%, respectively. No changes were observed on the concentrations of GABA, glutamine and taurine. The cysteine oxidation products, cysteine sulfinate (0.5 μM) and cystine (0.25 mM) were without effects. The effect of cysteine (0.5 mM) was dramatically reduced in media with no added bicarbonate/CO2. Thus, cysteine in a bicarbonate-sensitive manner selectively increases the extracellular concentration of excitotoxic amino acids in adult rat brain in vitro, possibly by interfering with the carrier-mediated glutamate uptake/ release
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| 7. |
- Bentzer, Peter, et al.
(författare)
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Supersensitivity in rat micro-arteries after short-term denervation
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 161:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
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| 8. |
- Curmi, J P, et al.
(författare)
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The influence of membrane potential on chloride channels activated by GABA in rat cultured hippocampal neurons.
- 1993
-
Ingår i: Journal of Membrane Biology. - 0022-2631 .- 1432-1424. ; 136:3, s. 273-80
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Tidskriftsartikel (refereegranskat)abstract
- Chloride currents were activated by a low concentration of GABA (0.5 microM) in neonatal rat hippocampal neurons cultured for up to 14 days. Currents elicited by 0.5 microM GABA in neurons, voltage-clamped using the whole-cell technique with pipettes containing 149 mM Cl-, reversed close to 0 mV whether pipettes contained 144 mM Na+ or 140 mM Cs+, and were blocked by 100 microM bicuculline. Current-voltage curves showed outward rectification. Single channel currents appeared in cell-attached patches when the pipette tip was perfused with pipette solution containing 0.5 microM GABA and disappeared when a solution containing 100 microM bicuculline plus 0.5 microM GABA was injected into the pipette tip. The channels showed outward rectification and, in some patches, had a much lower probability of opening at hyperpolarized potentials. The average chord conductance in 10 patches hyperpolarized by 80 mV was 7.8 +/- 1.6 pS (SEM) compared with a chord conductance of 34.1 +/- 3.5 pS (SEM) in the same patches depolarized by 80 mV. Similar single channel currents were also activated in cell-free, inside-out patches in symmetrical chloride solutions when 0.5 microM GABA was injected into the pipette tip. The channels showed outward rectification similar to that seen in cell-attached patches, and some channels had a lower probability of opening at hyperpolarized potentials. The average chord conductance in 13 patches hyperpolarized by 80 mV was 11.8 +/- 2.3 pS (SEM) compared with 42.1 +/- 3.1 pS (SEM) in the same patches depolarized by 80 mV.
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| 9. |
- Vinter-Jensen, Lars, et al.
(författare)
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Acute contractile effects of epidermal growth factor on bladder smooth muscles. An in vivo and in vitro study in rats
- 1997
-
Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 31:3, s. 231-235
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Tidskriftsartikel (refereegranskat)abstract
- Chronic treatment with epidermal growth factor (EGF) stimulates growth of all wall layers of the urinary tract in pigs and rats. Herein, we investigated the acute effects of EGF on detrusor smooth muscle activity. For in vivo examination, awake rats received EGF (75 micrograms/kg) intravenously and detrusor smooth muscle activity was monitored cystometrically. The EGF bolus caused no alteration in diuresis but a doubling of the micturition frequency, a 25% increase in micturition pressures, and increased irregular baseline contractile activity. For in vitro examination detrusor smooth muscle strips were exposed to EGF (1 microgram/ml). EGF caused contraction and increase in the spontaneous activity. In conclusion, EGF increases rat detrusor smooth muscle contractile activity in vivo and in vitro. The finding suggests that a direct effect of EGF on bladder smooth muscles is part of the genesis to the growth of the detrusor smooth muscle observed after chronic EGF treatment.
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| 10. |
- Grundemar, L, et al.
(författare)
-
Long-lasting inhibition of the cardiovascular responses to glutamate and the baroreceptor reflex elicited by neuropeptide Y injected into the nucleus tractus solitarius of the rat
- 1991
-
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 122:1, s. 135-139
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) microinjected unilaterally into the nucleus tractus solitarii (NTS) of anesthetized paralyzed rats elicits a gradual dose-dependent and reversible fall in arterial pressure (AP) and heart rate (HR) lasting 20 min. It also abolished the brief (less than 1 min) dose-dependent and reversible fall of AP and HR elicited by L-glutamate (L-Glu) injected into the nucleus. The blockade of L-Glu by NPY appeared gradually and was prolonged, lasting over 2 h, and recovering by 24 h. It was not replicated by desamido-NPY or galanin. Unlike 2% lidocaine it did not block the hypotension elicited by focal electrical stimulation at the injection site indicating the response was not that of a local anesthetic. Bilateral injection of NPY into the NTS resulted, after an initial fall, in an elevation of AP (+48 +/- 10.6 mmHg). At this time the reflex bradycardia evoked by elevating AP with phenylephrine was markedly reduced. We conclude that in the NTS, NPY antagonizes the actions of L-Glu and may attenuate baroreceptor reflexes. Since the NTS is richly innervated by NPY neurons and contains many NPY binding sites and since primary baroreceptor afferents appear to be glutamatergic the results suggested that NPY may serve in NTS as a long-term regulator of baroreceptor reflex activity.
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| 11. |
- Zhang, Jianhua, 1961, et al.
(författare)
-
Involvement of the medial geniculate body in prepulse inhibition of acoustic startle.
- 1999
-
Ingår i: Psychopharmacology. - 0033-3158. ; 141:2, s. 189-96
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Tidskriftsartikel (refereegranskat)abstract
- Prepulse inhibition of acoustic startle is the normal reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Previous studies have shown that several neuroanatomical structures and pathways in the brain are involved in the modulation of prepulse inhibition. In the present study, the functional importance of the medial geniculate body (MG) in the modulation of prepulse inhibition was investigated. To this end, in vivo brain microdialysis probes were used to infuse drugs locally into the MG of awake, freely moving rats simultaneously with startle response and prepulse inhibition measurements in the same animals. Intrageniculate infusion of the sodium channel blocker, tetrodotoxin, significantly reduced prepulse inhibition without affecting baseline startle amplitude. A similar effect was obtained after intrageniculate infusion of the GABA(B) receptor agonist, baclofen. In addition, intrageniculate infusion of muscimol, an agonist at the GABA(A) receptor complex, reduced prepulse inhibition, although this effect was obtained at a higher concentration of the drug compared to that of baclofen. These studies suggest that the MG is involved in the modulation of prepulse inhibition and that auditory signals relayed via the MG may be subjected to inhibitory control at this level, involving GABA neurotransmission.
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| 12. |
- Visse, E, et al.
(författare)
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Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-gamma, interleukin-7, or B7-1-transfected tumor cells
- 1999
-
Ingår i: Cancer Gene Therapy. - : Springer Science and Business Media LLC. - 0929-1903 .- 1476-5500. ; 6:1, s. 37-44
-
Tidskriftsartikel (refereegranskat)abstract
- Progress in the definition of the roles of various costimulators and cytokines in determining the type and height of immune responses has made it important to explore genetically altered tumor cells expressing such molecules for therapeutic immunizations. We have studied the effect of therapeutic subcutaneous (s.c.) immunizations on the growth of preexisting intracerebral brain tumor isografts in the rat. Transfectant glioma cell clones expressing either rat interferon-gamma (IFN-gamma), rat interleukin-7 (IL-7), or rat B7-1 were selected. After irradiation (80 Gy) the clones were used for immunization (administered in up to four s.c. doses in a hind leg over 14-day intervals starting 1 day after the intracranial isografting of the parental tumor). Significant growth inhibition of the intracerebral parental tumors was induced by transfectants expressing IFN-gamma and IL-7, respectively. The strongest effect was observed with IFN-gamma-expressing cells, resulting in cures in 37% of the males and in 100% of the females. Immunization with IL-7 had a similar, strong initial effect, with significantly prolonged survival in the majority of the rats but a lower final cure rate (survival for >150 days). The B7-1-expressing tumor clones induced cures in seven of eight female rats; however, no cures were seen in the male rats. It was also shown that the B7-1-expressing cells were themselves strongly immunogenic in female rats, requiring high cell numbers to result in a progressively growing tumor upon s.c. isografting; this was not the case in male rats. As a whole, the results imply that despite the unfavorable location of intracerebral tumors, therapeutic s.c. immunizations with certain types of genetically altered tumor cells can induce complete regressions with permanent survival and without gross neurological or other apparent signs of brain damage. The present results demonstrate complete regressions when immunizations are initiated shortly after intracranial isografting, when the intracerebral tumor is small.
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| 13. |
- Agardh, Carl-David, et al.
(författare)
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The influence of hypothermia on hypoglycemia-induced brain damage in the rat
- 1992
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Ingår i: Acta Neuropathologica. - 1432-0533. ; 83:4, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- The effects of hypothermia on hypoglycemic brain damage were studied in rats after a 30-min period of hypoglycemic coma, defined as cessation of spontaneous EEG activity. The rats were either normothermic (37 degrees C) or moderately hypothermic (33 degrees C). Morphological brain damage was evaluated after various periods of recovery. Hypothermic animals with halothane anesthesia never resumed spontaneous respiration, thus requiring artificial ventilation during recovery (maximally 8 h). In contrast, when isoflurane was used as the anesthetic agent, all animals survived and were examined after 1 week of recovery. There was a tendency towards gradually higher arterial plasma glucose levels during hypoglycemia with lower body temperature. The time period from insulin injection until isoelectric EEG appeared was gradually prolonged by hypothermia, and was shorter when isoflurane was used for anesthesia. Brain damage was examined within the neocortex, caudoputamen and hippocampus (CA1, subiculum and the tip of the dentate gyrus). Damage to neurons was found to be of two types, namely condensed dark purple neurons (pre-acidophilic) and shrunken bright red-staining neurons (acidophilic). In the neocortex, no clear influence of temperature on the degree of injury was seen. In the caudoputamen, the number of injured neurons clearly decreased at lower temperature (33 degrees C, P less than 0.001) when halothane was used, while no such difference was seen when isoflurane was used as the anesthetic agent. Likewise, a protective effect of hypothermia was seen in subiculum (P less than 0.01) when halothane, but not isoflurane was used.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 14. |
- Alheim, K, et al.
(författare)
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Interleukin 1 expression is inducible by nerve growth factor in PC12 pheochromocytoma cells.
- 1991
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 88:20, s. 9302-6
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the cytokine interleukin 1 alpha (IL-1 alpha) was demonstrated in the rat PC12 pheochromocytoma cell line by (i) immunohistochemistry using rabbit polyclonal antisera raised against the recombinant murine IL-1 alpha, (ii) an ELISA, and (iii) a specific cell conversion bioassay based on the use of LBRM33-1A5 cells. IL-1 alpha mRNA was demonstrated in the PC12 cells, by PCR amplification. Constitutive expression of IL-1 alpha in PC12 cells was demonstrated in all experiments, although the cellular levels of IL-1 alpha-like immunoreactivity varied. The expression of IL-1 alpha, as studied at the mRNA level, was inducible by mouse nerve growth factor (7S NGF), and the gene product level was inducible in a dose- and time-dependent fashion by 7S NGF. The maximum induction corresponds to a 600% increase in IL-1 alpha-like immunoreactivity above the expression level found in noninduced cells and occurred after a 3-day incubation of the cells with NGF at 0.75 micrograms/ml of culture medium. The significance of the ability of NGF to induce IL-1 expression lies in the fact that IL-1 itself also acts as a growth factor that promotes glial proliferation and, even more importantly, IL-1 itself induces the expression of NGF at peripheral nerve injury [Lindholm, D., Heumann, R., Meyer, M. & Thoenen, H. (1987) Nature (London) 330, 658-659].
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Anderson, Kevin J., et al.
(författare)
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Ischemia-induced upregulation of excitatory amino acid transport sites
- 1993
-
Ingår i: Brain Research. - 0006-8993. ; 622:1-2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- The response of excitatory amino acid transporter binding sites in the rat brain to 10 min of cerebral ischemia induced by bilateral common carotid occlusion combined with hypotension was examined. We observed a transient increase in the density of transporter binding sites that was first noticeable at 5 min post-recovery and persisted for 48 h. The increase in binding sites was found throughout the brain, but was most prevalent in hippocampus and other cortical regions. We conclude that delayed neuronal death following transient cerebral ischemia may not be due to a decrease in the number of excitatory amino acid transport sites.
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| 19. |
- Andreasen, N, et al.
(författare)
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Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment
- 1999
-
Ingår i: Neuroscience Letters. - 0304-3940. ; 273:1, s. 5-8
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Tidskriftsartikel (refereegranskat)abstract
- We studied CSF-tau and CSF-Abeta42 in 16 patients with mild cognitive impairment (MCI) who at follow-up investigations 6-27 months later had progressed to Alzheimer's disease (AD) with dementia. For comparison, we studied 15 age-matched healthy individuals. At baseline, 14/16 (88%) of MCI patients had high CSF-tau and/or low CSF-Abeta42 levels. These findings show that these CSF-markers are abnormal before the onset of clinical dementia and that they may help to identify MCI patients that will develop AD. This is especially important when drugs with potential effects on the progression of AD will reach the clinical phase.
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| 20. |
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| 21. |
- Beding-Barnekow, B., et al.
(författare)
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Systemic and intraocular uptake of spantide, a tachykinin antagonist, following topical application to the rabbit eye.
- 1990
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Ingår i: Experimental Eye Research. - 0014-4835. ; 50:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Previous observations have indicated that topical application to the rabbit eye of tachykinin antagonists, including spantide, effectively prevents the miosis and the disruption of the blood-aqueous barrier consequent to ocular injury. The present study shows that spantide is taken up into the rabbit eye following topical application. This was established by determination of spantide in the aqueous humor by radioimmunoassay. The concentrations reached in the aqueous humor were those that could be expected to block tachykinin receptors. The elimination of spantide from the aqueous humor was found to be slow. From HPLC analysis it seemed that spantide in the aqueous humor is degraded to smaller products, predominantly spantide 5–11. Some of the topically applied peptide appeared in the general circulation. Here the rate of elimination was rapid by comparison. Very small amounts of spantide appeared in the cerebrospinal fluid after intravenous injection.
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| 22. |
- Bengzon, J, et al.
(författare)
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Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling
- 1993
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Ingår i: Neuroscience. - 0306-4522. ; 53:2, s. 433-446
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Tidskriftsartikel (refereegranskat)abstract
- Levels of messenger RNA for nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and the tyrosine kinase receptors trkA, trkB and trkC have been studied using in situ hybridization in the rat brain 2 h and four weeks after kindling-induced seizures. Epileptiform activity evoked by hippocampal stimulation and exceeding 70 s lead to a concomitant and transient increase of brain- derived neurotrophic factor, nerve growth factor, trkB and trkC messenger RNA expression in dentate granule cells after both focal and generalized seizures. Brain-derived neurotrophic factor messenger RNA levels were also increased bilaterally in the CA1-CA3 regions, amygdala and the piriform, entorhinal, perirhinal, retrosplenial and temporal cortices after generalized seizures. The magnitude of the increases was similar throughout the development of kindling and in the fully kindled brain. No changes of trkA messenger RNA were observed. In amygdalar kindling, elevated brain-derived neurotrophic factor messenger RNA levels developed more rapidly in the amygdala-piriform cortex than after stimulation in the hippocampus but changes in the hippocampal formation were only seen in few animals. Intraventricular 6-hydroxydopamine or a bilateral fimbria-fornix lesion did not alter basal expression or seizure-evoked changes in messenger RNA levels for neurotrophins or trk receptors but increased the number of animals exhibiting elevated levels after the first stimulation, probably due to a prolongation of seizure activity. Both in sham-operated and fimbria-fornix-lesioned rats seizure activity caused a marked reduction of neurotrophin-3 messenger RNA levels in dentate granule cells. The results indicate that activation of the brain-derived neurotrophic factor gene, at least in dentate granule cells, is an "all-or-none" type of response and dependent on the duration but not the severity of seizures or the stage of kindling epileptogenesis. Changes in brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and trkB and trkC were observed concomitantly in the dentate gyrus, which suggests that seizure activity sets in motion a cascade of genomic events possibly mediated via a common mechanism. Since altered messenger RNA levels outside hippocampus were detected only for brain-derived neurotrophic factor, neurotrophin and trk gene expression in these regions seems to be regulated differently.
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| 23. |
- Bengzon, Johan, et al.
(författare)
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Regulation of norepinephrine transporter and tyrosine hydroxylase mRNAs after kainic acid-induced seizures
- 1999
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Ingår i: Brain Research. - 0006-8993. ; 842:1, s. 239-242
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Tidskriftsartikel (refereegranskat)abstract
- Noradrenergic locus coeruleus (LC) efferents to the forebrain suppress seizures in several models of epilepsy. Using in situ hybridization, we demonstrate that tyrosine hydroxylase (TH) and norepinephrine transporter (NET) but not vesicular monoamine transporter 2 (VMAT2) mRNA levels are transiently elevated in LC neurons following kainic acid-induced status epilepticus. These increases of TH and NET mRNAs and presumably of the proteins themselves might enhance synthesis and reuptake of NE postictally.
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| 24. |
- Bengzon, Johan, et al.
(författare)
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Suppression of epileptogenesis by modification of N-methyl-D-aspartate receptor subunit composition
- 1999
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X. ; 11:3, s. 916-922
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Tidskriftsartikel (refereegranskat)abstract
- The effects of altered N-methyl-D-aspartate (NMDA) receptor subunit composition on seizure development in kindling epilepsy were assessed in transgenic mice expressing high neuronal levels of NR2D under control of the calcium/calmodulin kinase II alpha subunit (αCaMKII) promoter. The NR2D subunit is normally present at very low levels in the mature forebrain. Transgenic mice showed a marked reduction of amygdala kindling development. Spread of epileptic activity was retarded acid generalized seizures appeared later in animals overexpressing NR2D compared with wild-type mice. The progressive lengthening of epileptiform activity, which normally occurs in kindling, was also dampened in transgenic animals. We conclude that NMDA receptor subunit composition determines the progression of experimental epilepsy.
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| 25. |
- Bergquist, Filip, 1970, et al.
(författare)
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Effects of local administration of L-, N-, and P/Q-type calcium channel blockers on spontaneous dopamine release in the striatum and the substantia nigra: a microdialysis study in rat.
- 1998
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Ingår i: Journal of neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 70:4, s. 1532-40
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Tidskriftsartikel (refereegranskat)abstract
- The pivotal role for voltage-sensitive calcium channels in initiating synaptic transmitter release is undisputed, but it is only partly known to what extent the different subtypes contribute in vivo. Their importance for the dendritic release of dopamine has not been investigated in vivo previously. To evaluate comprehensively the relative importance of different voltage-sensitive calcium channel subtypes for striatal dopamine release, and to further investigate the mechanism of dendritic dopamine release in the reticulate part of substantia nigra, dopamine was measured by in vivo microdialysis in the striatum or substantia nigra of awake rats. The calcium channel blockers nimodipine, omega-conotoxin-GVIA, omega-agatoxin-IVA, and neomycin were administered locally through the dialysis probes and compared with calcium-free perfusion. Results indicate that dopamine release in the striatum is mainly dependent on N- and P/Q-type channels, but the dendritic dopamine release in the substantia nigra is mediated mainly by some other calcium-dependent mechanism, for example, calcium mobilization through T-, O-, or R-type calcium channels. A portion of the dendritic release is calcium independent but can be inhibited partially by neomycin, which might suggest a role for inositol 4,5-bisphosphate breakdown products.
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| 26. |
- Bergstedt, K., et al.
(författare)
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Changes in insulin-like growth factor 1 receptor density after transient cerebral ischemia in the rat : Lack of protection against ischemic brain damage following injection of insulin-like growth factor 1
- 1993
-
Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 13:5, s. 895-898
-
Tidskriftsartikel (refereegranskat)abstract
- Binding of 125I-insulin-like growth factor-1 (125I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA1 and CA3 regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intracerebroventricular injections of IGF-1 (2 μg) prior to and after transient cerebral ischemia did not reduce neuronal damage. The increased up-regulation on IGF-1 receptors and the absence of neuroprotection by IGF-1 suggest that the intracellular signal transduction chain activated by the IGF-1 receptor may be interrupted.
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| 27. |
- Bergstedt, Kerstin, et al.
(författare)
-
Initiation of protein synthesis and heat-shock protein-72 expression in the rat brain following severe insulin-induced hypoglycemia
- 1993
-
Ingår i: Acta Neuropathologica. - 0001-6322. ; 86:2, s. 145-153
-
Tidskriftsartikel (refereegranskat)abstract
- Following stress such as heat shock or transient cerebral ischemia, global brain protein synthesis initiation is depressed through modulation of eucaryotic initiation factor (eIF) activities, and modification of ribosomal subunits. Concomitantly, expression of a certain class of mRNA, heat-shock protein (HSP) mRNA, is induced. Here we report that the activity of eucaryotic initiation factor-2 (eIF-2), a protein that participates in the regulation of a rate-limiting initiation step of protein synthesis, transiently decreases following insulin-induced severe hypoglycemia in the rat brain neocortex. Expression of HSP 72, a 72-kDa HSP, in surviving neurons was seen at 1-7 days of recovery following 30 min of hypoglycemic coma, but not at 1 h and 6 h of recovery. In the neocortex, HSP 72 was first seen in layer IV, and later also in surviving neurons in layer II. In the CA1 region and in the crest of dentate gyrus, HSP 72 expression was evident in cells adjacent to irreversibly damaged neurons. In the CA3 region and the hilus of dentate gyrus, HSP 72 was expressed in a few scattered neurons. In septal nucleus, HSP 72 was expressed in a lateral to medial fashion over a period of 1-3 days of recovery. We conclude that severe insulin-induced hypoglycemia induces a stress response in neurons in the recovery phase, including inhibition of protein synthesis initiation, depression of eIF-2 activity, and a delayed and prolonged expression of HSP 72 in surviving neurons. The HSP 72 expression may be a protective response to injurious stress.
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| 28. |
- Bergstedt, Kerstin, et al.
(författare)
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Postischaemic changes in protein synthesis in the rat brain : effects of hypothermia
- 1993
-
Ingår i: Experimental Brain Research. - 0014-4819. ; 95:1, s. 91-99
-
Tidskriftsartikel (refereegranskat)abstract
- Protein synthesis, measured as [14C]-leucine incorporation into proteins, was studied in the normothermic rat brain following 15 min of transient cerebral ischaemia and 1 h, 24 h and 48 h of recirculation, and in the hypothermic (33°C) brain following 1 h and 48 h of recirculation. Ischaemia was induced by bilateral common carotid occlusion combined with hypotension. Following normothermic ischaemia, incorporation of [14C]-leucine was depressed by 40-80% at 1 h of recirculation in all brain regions studied. At 48 h postischaemia, incorporation returned to normal or above normal levels in the inner layers of neocortex, the CA3 region, the striatum and the dentate gyrus, while in the outer layers of neocortex and in the hippocampal CA1 region the incorporation was persistently decreased by 26% and 40% respectively. At 24 and 48 h postischaemia, protein synthesis in the CA1 region and the striatum could be attributed to proliferating microglia. Intra-ischaemic hypothermia ameliorated the persistent depression of protein synthesis in the CA1 region at 48 h postischaemia, and a two-fold increase compared to the normothermic group was observed both in the CA1 region and the striatum. In the cortex, eucaryotic initiation factor 2 activity transiently decreased at 30 min postischaemia. In animals subjected to intra-ischaemic hypothermia, the eucaryotic initiation factor 2 activity was reduced by 50% of control at 30 min of recirculation compared with 77% in normothermic animals. We conclude that the postischaemic depression of protein synthesis is in part caused by a decrease in eucaryotic initiation factor 2 activity. The early postischaemic depression may reflect a reaction of the tissue to stress, while the late persistent depression, which is normalised by intra-ischaemic hypothermia, may be related to the mechanism of cell death.
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| 29. |
- Björklund, A, et al.
(författare)
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Reafferentation of the subcortically denervated hippocampus as a model for transplant-induced functional recovery in the CNS
- 1990
-
Ingår i: Progress in Brain Research. - 0079-6123. ; 83, s. 411-426
-
Forskningsöversikt (refereegranskat)abstract
- Subcortical deafferentation of the hippocampal formation is known to induce profound behavioural deficits. Transplants of fetal septal or brainstem tissue are capable of restoring some aspects of normal physiological and behavioural function in subcortically deafferented (i.e. fimbria-fornix or septal lesioned) rats. Such grafts have been shown to re-establish extensive new afferent inputs to the denervated hippocampal formation. As shown for grafted cholinergic and noradrenergic neurons, the ingrowing axons form laminar innervation patterns which closely mimic those of the normal cholinergic and noradrenergic innervations. The ingrowth appears to be very precisely regulated by the denervated target: each neuron type produces distinctly different innervation patterns; the growth is inhibited by the presence of an intact innervation of the same type; and it is stimulated by additional denervating lesions. Both ultrastructually and electrophysiologically the graft-derived fibres have been seen to form extensive functional synaptic contacts. Biochemically, cholinergic septal grafts and noradrenergic locus coeruleus grafts restore transmitter synthesis and turnover in the reinnervated hippocampus. Intracerebral microdialysis has revealed that acetylcholine and noradrenaline release is restored to normal or supranormal levels in the graft-reinnervated hippocampus, and that the grafted neurons can be activated in a normal way from the host through behavioural activation induced by sensory stimulation or electrical stimulation of the lateral habenula. These results indicate that the grafted monoaminergic neurons can restore tonic regulatory neurotransmission at previously denervated synaptic sites even when they are implanted into the ectopic brain sites. Such functional reafferentation may be sufficient for at least partial restoration of function in the subcortically deafferented hippocampus.
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| 30. |
- Björklund, Anders, et al.
(författare)
-
Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease
- 1997
-
Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 4:3-4, s. 186-200
-
Forskningsöversikt (refereegranskat)abstract
- Intrastriatal 6-hydroxydopamine injections in rats induce partial lesions of the nigrostriatal dopamine (DA) system which are accompanied by a delayed and protracted degeneration of DA neurons within the substantia nigra. By careful selection of the dose and placement of the toxin it is possible to obtain reproducible and regionally defined partial lesions which are well correlated with stable functional deficits, not only in drug-induced behaviors but also in spontaneous motoric and sensorimotoric function, which are analogous to the symptoms seen in patients during early stages of Parkinson's disease. The intrastriatal partial lesion model has proved to be particularly useful for studies on the mechanisms of action of neurotrophic factors since it offers opportunities to investigate both protection of degenerating DA neurons during the acute phases after the lesion and stimulation of regeneration and functional recovery during the chronic phase of the postlesion period when a subset of the spared nigral DA neurons persist in an atrophic and dysfunctional state. In the in vivo experiments performed in this model glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neurotrophic effects both at the level of the cell bodies in the substantia nigra and at the level of the axon terminals in the striatum. Intrastriatal administration of GDNF appears to be a particularly effective site for induction of axonal sprouting and regeneration accompanied by recovery of spontaneous sensorimotor behaviors in the chronically lesioned nigrostriatal dopamine system.
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| 31. |
- Blay, Pilar, et al.
(författare)
-
An in vivo study of the effect of 5-HT and sympathetic nerves on transferrin and transthyretin mRNA expression in rat choroid plexus and meninges
- 1994
-
Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 662:1-2, s. 148-154
-
Tidskriftsartikel (refereegranskat)abstract
- Brain expression of transferrin (Tf) and transthyretin (TTR) mRNA has been demonstrated in different species, TTR being found only in the choroid plexus. We report here that both these mRNAs are also expressed in the meninges. In vitro studies have shown that Tf secretion by the rat choroid plexus is stimulated by 5-hydroxytryptamine (5-HT) while sympathetic nerves regulate different transport functions in the same tissue. We have used various in vivo models to study the neuroendocrine regulation of Tf and TTR mRNA expression in the choroid plexus and meninges. Destruction of the serotonergic nerves in the brain by either raphe nuclei lesion or intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), which both decreased brain 5-HT levels significantly, did not affect Tf or TTR mRNA levels in choroid plexus and meninges, but increased TTR mRNA in liver. Intraventricular injection of 10 or 100 pmol 5-HT did not change the expression of these proteins in any of the tissues studied. Removal of the sympathetic innervation to the choroid plexus by cervical sympathectomy did not affect Tf or TTR mRNA levels in choroid plexus and liver, nor the incorporation of radioactive leucine into protein in various parts of the brain. In conclusion, our results do not support a regulatory role in vivo for neuronally derived 5-HT or sympathetic nerve activity on Tf and TTR mRNA expression in rat choroid plexus and meninges.
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| 32. |
- Blay, P, et al.
(författare)
-
Transthyretin expression in the rat brain: effect of thyroid functional state and role in thyroxine transport
- 1993
-
Ingår i: Brain Research. - 1872-6240. ; 632:1-2, s. 114-120
-
Tidskriftsartikel (refereegranskat)abstract
- Rats were made hypo- or hyperthyroid to study the role of thyroid hormones on cerebral transthyretin (TTR) mRNA expression. TTR mRNA was detected by Northern blot in rat liver, choroid plexus and meninges but not in cultured astrocytes or cultured cerebral endothelial cells. No changes were found in the levels of TTR mRNA in liver, choroid plexus or meninges in hypo- or hyperthyroid rats compared with the controls. In order to investigate the main route of thyroxine transport from blood to brain, the distribution of [125I]thyroxine in the brain was studied after intravenous (i.v.) and intraventricular (i.v.c.) injection by both direct counting and autoradiography. While distribution of [125I]thyroxine could be seen throughout the brain parenchyma after i.v. injection, the labelling was confined to the CSF spaces after i.v.c. administration. When protein synthesis was inhibited by cycloheximide treatment and [125I]thyroxine was injected intravenously, the uptake of [125I]thyroxine in the choroid plexus decreased while the uptake in the cerebral cortex increased. This indicates that thyroxine is transported into the brain primarily through the blood-brain barrier and not via the choroid plexus and CSF. We discuss the possibility that TTR has a role in the distribution of thyroxine throughout the brain.
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| 33. |
- Boström, Ola, 1963, et al.
(författare)
-
A new neck injury criterion candidate-based on injury findings in the cervical spinal ganglia after experimental neck extension trauma
- 1996
-
Ingår i: PROCEEDINGS OF THE 1996 INTERNATIONAL IRCOBI CONFERENCE ON THE BIOMECHANICS OF IMPACT, SEPTEMBER 11-13, DUBLIN, IRELAND. ; , s. 123-136
-
Konferensbidrag (refereegranskat)abstract
- In this study a mathematical model, based on Navier Stokes equations, was developed and validated against experimental data. This model predicts the pressure changes in the spinal canal as a function of the volume change inside the canal during neck bending in the x-z (sagittal) plane. Another aim of the study was to investigate pressure phenomena and ganglion injuries at static neck extension loading and dynamic neck extension trauma with a head-restraint present. Experiments on pigs were conducted. Preliminary results indicate that ganglion injuries, as well as pressure transients inside the spinal canal, seem to correlate to the phase shift when the neck passes an s-shape (or maximal retraction) during the rearward motion of the head. That is, when the upper neck quickly changes from a flexion to an extension shape. Static loading of the neck resulted in no signs of injuries to the ganglia. A possible candidate for a neck injury criterion is presented, based on the relative acceleration between the top and the bottom of the cervical spine. A tolerance level based on the pig tests is also discussed.
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| 34. |
- Breidbach, O, et al.
(författare)
-
Common general morphological pattern of peptidergic neurons in the arachnid brain : crustacean cardioactive peptide-immunoreactive neurons in the protocerebrum of seven arachnid species.
- 1995
-
Ingår i: Cell and Tissue Research. - 0302-766X .- 1432-0878. ; 279:1, s. 183-197
-
Tidskriftsartikel (refereegranskat)abstract
- A polyclonal antiserum raised against crustacean cardioactive peptide labels 14 clusters of immunoreactive neurons in the protocerebrum of the spiders Tegenaria atrica and Nephila clavipes, and the harvestman (opilionid) Rilaena triangularis. In all species, these clusters possess the same number of neurons, and share similar structural and topological characteristics. Two sets of bilateral symmetrical neurons associated with the optic lobes and the arachnid "central body" were analysed in detail, comparing the harvestman R. triangularis and the spiders Brachypelma albopilosa (Theraphosidae), Cupiennius salei (Lycosidae), Tegenaria atrica (Agelenidae), Meta segmentata (Metidae) and Nephila clavipes (Araneidae). Sixteen neurons have been identified that display markedly similar axonal pathways and arborization patterns in all species. These neurons are considered homologues in the opilionid and the araneid brains. We presume that these putative phylogenetically persisting neurons represent part of the general morphological pattern of the arachnid brain.
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| 35. |
- Brundin, Patrik, et al.
(författare)
-
Graft survival
- 1999
-
Ingår i: Journal of Neurosurgery. - 0022-3085. ; 90:4, s. 804-805
-
Tidskriftsartikel (refereegranskat)
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| 36. |
- Brundin, Patrik, et al.
(författare)
-
Grafts of Embryonic Dopamine Neurons in Rodent Models of Parkinson's Disease
- 1999
-
Ingår i: CNS regeneration: Basic Science and Clinical Applications. - 9780127050706 ; , s. 299-299
-
Bokkapitel (refereegranskat)abstract
- This chapter exemplifies rodent models of Parkinson's disease that have been used in transplantation studies and recounts basic transplantation methods. It describes morphological features of grafts containing dopamine neurons and focuses on the role of nigral grafts that are implanted homotopically in the mesencephalon, for example, near their location in the normal brain. The neurotoxin 6-hydroxydopamine (OHDA) is selectively taken up by catecholaminergic neurons and kills them through a mechanism that is still not fully elucidated, but may well include oxidative stress. When injected in adequate amounts into the brain, it can cause extensive and permanent damage to catecholaminergic neurons, such as those giving rise to the nigrostriatal pathway. The survival of dopamine neurons placed in a 6-OHDA denervated striatum is reflected by restoration of striatal dopamine levels to around 10 to 30% of normal. Examination of the ratio between levels of the dopamine metabolite DOPAC and dopamine reveals ratios that are 50 to 200% higher in grafted striata compared to normal, suggesting that the grafted neurons have an increased transmitter turnover
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| 37. |
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| 38. |
- Cardell, Monika, et al.
(författare)
-
Protein kinase C is translocated to cell membranes during cerebral ischemia
- 1990
-
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 119:2, s. 228-232
-
Tidskriftsartikel (refereegranskat)abstract
- The subcellular distribution of PKC(α) and PKC(γ) was studied in homogenates of cerebral cortex from rats subjected to 10 and 15 min of ischemia and 15 min of ischemia followed by 1 h, 6 h, 24 h, 48 h, and 7 days of reperfusion. During ischemia no significant changes in the levels of PKC (α) were seen. During the first hour of reperfusion, a transient 2.5-fold (P < 0.05) increase in PKC(α) levels was observed in the particulate fraction. In contrast, a three-fold increase of PKC(γ) in the particulate fraction concomitant with a 40% decrease in the cytosol was noted during ischemia. In the postischemic phase the levels in the cytosol decreased to 35% of control values at 2 days following ischemia, with a concomitant decrease in the particulate fraction to control levels. The redistribution of PKC to the cell membranes during and following ischemia could be due to ischemia induced receptor activation, increased levels of diacylglycerols, arachidonate and intracellular calcium, and may be of importance for the development of ischemic neuronal damage.
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| 39. |
- Cardell, Monika, et al.
(författare)
-
Time Course of the Translocation and Inhibition of Protein kinase C During Complete Cerebral Ischemia in the Rat
- 1993
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 61:4, s. 1308-1314
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract: The time course for the ischemia‐induced changes in the subcellular distribution of protein kinase C (PKC) (α), (β311). and (γ) and the activity of PKC were studied in the neocortex of rats subjected to 1, 2, 3, 5, 10, and 15 min of global cerebral ischemia. In the particulate fraction, a 14‐fold increase in PKC (γ) levels was seen at 3 min of ischemia, which further increased at 5–15 min of ischemia. At 15 min of ischemia, PKC (γ) and (βll) levels had increased two‐ and six‐fold, respectively. In the cytosolic fraction, a transient early 1.4‐fold increase in PKC (βll) and PKC (γ) levels was seen, whereas no change in the levels PKC (α) was noted. PKC (γ) levels then progressively declined, reaching 50% at 15 min of ischemia. At 5 min of ischemia, a 43% decrease in PKC activity was seen in the particulate fraction, reaching 50% at 15 min of ischemia concomitant with a 27% decrease in the cytosolic fraction. There was no change in the activator‐independent PKC activity. Pretreatment with the ganglioside AGF2 prevented the redistribution of PKC (γ) in the particulate fraction at 5 min. but not at 10 min of ischemia. The observed time course for the translocation of PKC (γ) parallels the ischemia‐induced release of neurotransmitters and increased levels of diacylglycerols, arachidonate, and intra‐cellular calcium and delineates this subspecies as especially ischemia‐sensitive. Ganglioside pretreatment delayed the translocation of PKC (γ), possibly by counteracting the effects of ischemia‐induced factors that favor PKC binding to cell membranes.
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| 40. |
- Cenci, M A, et al.
(författare)
-
Characterization of in vivo noradrenaline release from superior cervical ganglia or fetal locus coeruleus transplanted to the subcortically deafferented hippocampus in the rat
- 1993
-
Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 122:1, s. 73-87
-
Tidskriftsartikel (refereegranskat)abstract
- Solid grafts of autologous superior cervical ganglia (SCG) or fetal locus coeruleus (LC) were implanted unilaterally into a fimbria-fornix lesion cavity adjacent to the hippocampal formation after a 6-hydroxydopamine lesion of the intrinsic noradrenergic system. Twelve to 15 months after transplantation, one microdialysis probe was implanted in the dorsal hippocampus ipsilateral to the graft, and extracellular levels of noradrenaline (NA) were monitored during the application of pharmacological or behavioral stimuli. Age-matched intact and lesion-only animals served as controls. Morphological examination of the grafts was performed on sections processed for dopamine-beta-hydroxylase (DBH) immunohistochemistry. In the lesion-only controls, the hippocampus was totally devoid of DBH-immunoreactive fibers and hippocampal levels of NA were generally undetectable. Although both SCG and LC grafts gave rise to an extensive DBH-immunoreactive fiber ingrowth in the ipsilateral hippocampus, baseline NA release was strikingly different in the two graft groups, being markedly lower than normal in the SCG-grafted rats (3.5 +/- 0.1 fmol/30 microliters) and significantly higher than normal in the LC-grafted rats (44.5 +/- 12.3 fmol/30 microliters). The response to potassium-induced depolarization (100 mM KCl in the perfusion fluid), neuronal uptake blockade (5 microM desipramine), and sodium-channel blockade (1 microM TTX) was similar to normal in both graft groups. Exposure of the animals to mild (handling) or severe (immobilization) stressful stimuli significantly enhanced NA release in the intact controls, whereas no clear-cut effect could be detected in either graft group. Electrical stimulation of the medial septum, applied in an attempt to activate possible afferents to the grafts from the host septum, did not enhance NA release in any of the groups. The results show that grafts of both central and peripheral noradrenergic neurons can provide a source of steady-state NA release in the denervated hippocampus, but that the spontaneous activity of the grafted ganglionic neurons is very low compared to that of the LC neurons, probably due to the absence of a functional preganglionic input to the grafted SCG neurons. Although extracellular NA recovered from both the SCG- and the LC-grafted hippocampi is likely to derive from impulse-dependent neuronal release, it was largely unaffected by physiological stimuli applied to the host.
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| 41. |
- Clarke, D J, et al.
(författare)
-
Synaptic connections formed by grafts of different types of cholinergic neurons in the host hippocampus
- 1990
-
Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 107:1, s. 11-22
-
Tidskriftsartikel (refereegranskat)abstract
- The present experiment was performed to determine whether different types of grafted central cholinergic neurons are able to form synaptic contacts with host hippocampal neurons. Grafts from the septal-diagonal band area, which contain the neurons that normally innervate the hippocampal formation, were compared to those from the nucleus basalis magnocellularis region (NBM), the striatum, the pontomesencephalic tegmentum of the brain stem, and the spinal cord. The regions were dissected from 14- to 16-day-old rat fetuses, and the same number of viable cells (35 x 10(4] from each of the different regions was stereotaxically injected as a cell suspension into the hippocampus of rats subjected to a complete fimbria-fornix lesion, transecting the intrinsic septohippocampal pathways. At 14 to 17 weeks after transplantation, the brains were processed for choline acetyltransferase (ChAT) immunocytochemistry at the light and electron microscopic levels and acetylcholinesterase (AChE) histochemistry at the light microscopic level. There was a great variation in the number of surviving ChAT-positive cells among the different graft types. The septal grafts contained the highest number of ChAT-positive cells, and the striatal grafts showed the lowest numbers. The NBM, brain stem, and spinal cord grafts were in between. The differences in the number of ChAT-positive neurons between the groups matched, in general, the differences found in the magnitude of graft-derived AChE-positive fiber growth into the host hippocampal formation. At the electron microscopical level, all types of grafts were capable of forming synaptic contacts with host elements, however, with vast differences in the number of synapses found. The septal grafts produced the highest number of contacts, whereas the striatal and spinal cord grafts produced very few contacts. The ultrastructure of the cholinergic fibers from grafts obtained from the forebrain areas, i.e., septum, NBM, and striatum all appeared normal, whereas brain stem and spinal cord grafts produced different types of anomalies. The results show that grafted cholinergic neurons, that normally do not innervate the hippocampus, can send axons and form synaptic contacts in the host hippocampus. The ability to reinnervate the denervated hippocampal target appears to be shared by the embryologically closely related forebrain cholinergic neuron types, i.e., the septal, NBM, and striatal neurons. The marked differences in overall fiber ingrowth and number of synapses observed between these different types of grafts could be explained largely on the basis of differences in survivability of each grafted neuron type. By contrast, the reinnervation obtained from the grafted brain stem and spinal cord neurons were both quantitatively and qualitatively abnormal.(ABSTRACT TRUNCATED AT 400 WORDS)
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| 42. |
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| 43. |
- Coimbra, Cicero, et al.
(författare)
-
Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an anti-inflammatory/antipyretic drug : Evidence for chronic encephalopathic processes following ischemia
- 1996
-
Ingår i: Stroke. - 0039-2499. ; 27:9, s. 1578-1585
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: It has been recognized that postischemic pharmacological interventions may delay the evolution of neuronal damage rather than provide long-lasting neuroprotection. Also, fever complicates recovery after stroke in humans. Here we report the effects of late postischemic treatment with hypothermia and an antipyretic/anti-inflammatory drug, dipyrone, on cell damage at 1 week and 2 months of survival. Methods: Rats were subjected to 10 minutes of forebrain ischemia hypothermia (33°C) was induced at 2 hours of recovery and maintained for 7 hours. Dipyrone (100 mg · kg-1 IP) was given every 3 hours from 14 to 72 hours of recovery. Temperature was measured every 6 hours for 60 days. Neuronal damage was assessed at 7 days and 2 months of recovery. Results: From 17 to 72 hours of recovery, a period of hyperthermia was observed, which dipyrone abolished but postischemic hypothermia treatment did not. Dipyrone treatment diminished neuronal damage by 43% at 7 days, and at 2 months of survival, a minor (16%) protection was seen. Postischemic hypothermia treatment alone delayed neuronal damaged. In contrast, combined treatment of hypothermia followed by dipyrone markedly diminished neuronal damage by more than 50% at both 7 days and 2 months of recovery. Conclusions: Neuronal degeneration may be ongoing for months after a transient ischemic insult, and prolonged protective measures need to be instituted for long-lasting neuroprotective effects. Hyperthermia during recovery worsens ischemic damage, and processes associated with inflammatory may contribute to the development of neuronal damage. An early and extended period of postischemic hypothermia provides a powerful and long-lasting protection if followed by treatment with anti- inflammatory/antipyretic drugs.
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| 44. |
- Coimbra, Cicero, et al.
(författare)
-
Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia
- 1994
-
Ingår i: Acta Neuropathologica. - 0001-6322. ; 87:4, s. 325-331
-
Tidskriftsartikel (refereegranskat)abstract
- Intraischemic moderate hypothermia generally protects the brain against ischemic cell death, while hypothermia instigated several hours into the reperfusion phase is considered to be less effective. Here we report the effect of hypothermia (32.5°-33.5°C) of 5-h duration, initiated at 2, 6, 12, 24 and 36 h into the recirculation phase following 10 min of transient cerebral ischemia, on ischemic neuronal injury in the hippocampus and striatum of the rat. Hypothermia induced at 2 h, and 6 h postischemia reduces neuronal damage in the entire hippocampal CA1 region by approximately 50%. In the lateral CA1 region hypothermia induced at 12 h postischemia, significantly mitigates necrosis. When initiated at 2 h postischemia, but not later, protection was also observed in the striatum. Hypothermia induced 24 and 36 h postischemia was ineffective. A period of hypothermia of 5 h, initiated 2 h postischemia, was required for marked neuronal protection in the CA1 region, while 3.5-h hypothermia decreased neuronal damage by approximately 10% and 30 min hypothermia was ineffective. The clinical implications of the data are that extended period of hypothermia initiated long into the recovery phase following ischemia may prove beneficial. Hypothermia protects brain regions displaying rapid as well as delayed neuronal damage, and a minimal time of hypothermia is required for effective neuronal protection. Also, strict temperature control for up to 24 h postischemia may be required for proper assessment of the efficacy of cerebro-protective drugs.
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| 45. |
- Dahlqvist, Per, et al.
(författare)
-
Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats
- 1999
-
Ingår i: Neuroscience. - 1873-7544 .- 0306-4522. ; 93:2, s. 527-535
-
Tidskriftsartikel (refereegranskat)abstract
- Housing rats in an enriched environment after focal brain ischemia improves functional outcome without changes in infarct volume, suggesting neuroplastic changes outside the lesion. In this study, permanent occlusion of the middle cerebral artery was followed by housing in an enriched or a standard environment. Nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression were determined by in situ hybridization two to 30 days after middle cerebral artery occlusion. Stroke induced a decrease in nerve growth factor-induced gene A messenger RNA expression in cortical areas outside the ischemic lesion and in the CA1 subregion of the hippocampus two to three days after ischemia. This decrease was more prolonged with environmental enrichment, lasting until 20 days. However, 30 days after focal cerebral ischemia, environmental enrichment increased nerve growth factor-induced gene A expression compared to standard housing. A reduction of hippocampal glucocorticoid receptor (type II) messenger RNA two to 12 days after stroke in standard housed rats was restored by environmental enrichment. These data suggest that improved functional outcome induced by environmental enrichment after middle cerebral artery occlusion is associated with dynamically altered expression of nerve growth factor-induced gene A messenger RNA in brain regions outside the ischemic lesion, and sustained levels of hippocampal glucocorticoid receptor messenger RNA expression.
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| 46. |
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| 47. |
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| 48. |
- De Barrio, M, et al.
(författare)
-
Fixed drug eruption induced by indapamide. Cross-reactivity with sulfonamides
- 1998
-
Ingår i: Journal of Investigational Allergology & Clinical Immunology. - 1698-0808. ; 8:4, s. 253-255
-
Tidskriftsartikel (refereegranskat)abstract
- Indapamide is a nontiazidic sulfonamide diuretic which has not been previously reported as a cause of fixed drug eruption. We describe a patient who experienced several episodes of fixed drug eruption during treatment with indapamide. The diagnosis was confirmed by positive controlled oral challenge test. The possible existence of cross-reactivity with other sulfonamide derivatives was investigated by controlled oral challenge test with sulfamethoxazole, sulfadiazine and furosemide, with the tests with sulfamethoxazole and sulfadiazine resulting positive.
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| 49. |
- Ding, Wei-Qun, et al.
(författare)
-
Ethanol exposure increases expression of c-jun and junD in human neuroblastoma cells
- 1996
-
Ingår i: NeuroReport. - 1473-558X. ; 7:13, s. 2191-2195
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the effect of ethanol exposure on the expression of fos and jun genes. Exposure of human neuroblastoma SH-SY5Y cells to ethanol for 2-4 days caused a dose-dependent increase in c-jun and junD mRNA levels, whereas mRNAs for c-fos, fosB and junB were not detectable in control or ethanol-treated cells. Four days of ethanol exposure also enhanced the AP-1 binding activity. Experiments with actinomycin D demonstrated that ethanol did not influence the degradation of c-jun and junD mRNAs. These results demonstrate that long-term exposure to ethanol increases c-jun and junD expression. This effect may be one of the mechanisms through which ethanol influences the gene regulatory system in neuronal cells.
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- Ding, Wei-Qun, et al.
(författare)
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Stimulation of muscarinic receptors induces expression of individual fos and jun genes through different transduction pathways
- 1998
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 70:4, s. 1722-1729
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Tidskriftsartikel (refereegranskat)abstract
- The transduction pathways coupling muscarinic receptors to induction of fos and jun genes were investigated in neuroblastoma SH-SY5Y cells. Stimulation with carbachol induced expression of c-fos, fosB, c-jun, junB, and junD. This effect was abolished by pretreatment with atropine, indicating an involvement of muscarinic receptors. These genes were also induced by activation of protein kinase C with phorbol ester or by elevating the intracellular Ca2+ concentration with a Ca2+ ionophore. The Ca2+ effect was inhibited by KN-62, suggesting an induction through Ca2+/calmodulin-dependent kinase II. Inhibition of protein kinase C with GF109203X suppressed the carbachol-stimulated increase in mRNA levels of c-fos, fosB, and junB by approximately 70% but had only minor effects on the expression of c-jun and junD. On the other hand, preincubation with KN-62 attenuated the carbachol-induced increase in c-jun and junD expression by 70% but had no effect on c-fos, fosB, and junB mRNA levels. Simultaneous inhibition of both protein kinase C and Ca2+/calmodulin-dependent kinase II completely abolished the carbachol-stimulated expression of c-jun and junD, but c-fos, fosB, and junB were still expressed to a certain extent under this condition. Comparison of the inhibitory effects of GF109203X and Go 6976 suggests the involvement of classical protein kinase C isozymes in muscarinic receptor-stimulated expression of fos and jun genes. These results demonstrate that the muscarinic receptor-induced expression of individual fos and jun genes is regulated via different pathways, primarily protein kinase C or Ca2+/calmodulin-dependent kinase II.
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