| 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
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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 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
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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
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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)
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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
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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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