| 1. |
- Clarke, D J, et al.
(författare)
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Synaptic connections formed by grafts of different types of cholinergic neurons in the host hippocampus
- 1990
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 107:1, s. 11-22
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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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| 2. |
- Doering, L C, et al.
(författare)
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Abnormal perikaryal immunoreactivity to the phosphorylated heavy neurofilament unit in intracerebral basal forebrain transplants
- 1991
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Ingår i: Experimental Neurology. - 0014-4886. ; 111:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Grafts of Embryonic Day 14-15 basal forebrain tissue (medial septal/diagonal band nuclei) were transplanted into an aspirative fimbria-fornix cavity or the hippocampus of young adult rats. After extended periods of survival (1 and 2 years) the grafts were examined with immunocytochemical probes to identify specific types of neurons and assess the (spatial) distribution of the phosphorylated heavy neurofilament protein. Subpopulations of the long-term transplanted neurons expressed immunoreactivity to choline acetyl-transferase (CAT) and the low-affinity nerve growth factor receptor (192-IgG). Axons from the grafted neurons, visualized with the monoclonal antibody RT97 to the Mr 200,000 phosphorylated neurofilament unit, were observed to extend over the surfaces of the brain and connect with the host hippocampus. In subgroups of neurons without apparent axonal connections to the hippocampus, a change from axonal to cell body RT97 immunoreactivity was evident. A population of these neurons with abnormal neurofilament immunostaining in the soma was simultaneously identified as cholinergic with the CAT antibody. These studies indicate that abnormal changes can develop in the cytoskeleton of neurons in long-term intracerebral septal transplants. Although the reasons for this type of neurofilament modification in the grafted neurons are unknown, inappropriate terminal connections may be an important factor in the expression of this cytoskeletal change.
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| 3. |
- Ekström, Peter, et al.
(författare)
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A morphometric study of age-related changes in serotonin-immunoreactive cell groups in the brain of the coho salmon, Oncorhynchus kisutch walbaum
- 1992
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Ingår i: Experimental Neurology. - 0014-4886. ; 116:2, s. 204-209
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Tidskriftsartikel (refereegranskat)abstract
- In the coho salmon there is a transient increase in total brain concentrations of serotonin during smolt transformation which occurs midlife, just before down-stream migration to the ocean. There is also a gradual age-related increase in total brain serotonin concentrations. These increases may be due to reorganization of the central serotonergic system, changes in serotonin turnover, or both. They may be related to the specific physiological conditions during different life stages of salmon, or to ongoing growth and plastic changes of the brain. In the present study we have compared serotonin-immunoreactive (5-HTir) cell groups in 1-year-old freshwater presmolt and 2-year-old seawater postsmolt salmon. Our data indicate a continuous growth of the 5-HTir cell groups in terms of an increase in numbers of 5-HTir neurons in the cell groups of the pretectum and the brain stem, and an increase in the volumes of such neurons and cell groups. However, when related to the increase in total brain volume, i.e., the volume that may be innervated by the 5-HTir neurons, the ratio of 5-HTir neurons per mm3 decreased. The largest decreases were observed in the median raphe nucleus (P < 0.005) and the B9 group (P < 0.05). The ratio of volumes of the brain nuclei containing 5-HTir neurons relative to total brain volume was remarkably constant when comparing pre- and postsmolt brains: only the pretectal nucleus showed a significant decrease (P < 0.01) in relative volume. The total volume of 5-HTir neurons increased in postsmolts (P < 0.005). Since there was no increase in size of 5-HTir somata in any nucleus, changes in total volume reflect the changes in numbers of 5-HTir neurons. Thus, to account for the observed age-related increase in total brain concentrations of serotonin, an increase in the net production of serotonin, possibly accompanied by an increase in the density of serotonergic innervation in certain brain areas, may be postulated. The transient surge of whole brain content of serotonin observed at smolt transformation probably reflects a transient change in serotonin metabolism rather than an increase in the number of neurons.
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| 4. |
- Grabowski, Martin, et al.
(författare)
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Fetal neocortical grafts implanted in adult hypertensive rats with cortical infarcts following a middle cerebral artery occlusion: ingrowth of afferent fibers from the host brain
- 1992
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Ingår i: Experimental Neurology. - 0014-4886. ; 116:2, s. 105-121
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Tidskriftsartikel (refereegranskat)abstract
- This study is focused on the survival of fetal neocortical grafts placed in the infarcted adult host cortex of the spontaneously hypertensive rat and describes the ability of host axonal regeneration into the graft after a focal ischaemic lesion. Five to seven days following ligation of the right middle cerebral artery, dissociated neocortical primordium from fetuses of gestational age 12-18 days was implanted into the infarcted cortical area. Surviving transplants were seen in all rats, although grafts derived from gestational age 12-14 days displayed an irregular morphology rich in sinusoid-like cavities and containing fewer cells of apparently mature neuronal morphology. Grafts from older donors contained perikarya of neuronal appearance; however, they lacked normal cortical lamination. Ten days postgrafting, fibers stained by acetylcholinesterase histochemistry, dopamine-beta-hydroxylase, and 5-hydroxytryptamine immunohistochemistry were found in the grafts, and by 10-23 weeks after transplantation the fiber density had increased substantially. When the retrograde tracer Fluoro-Gold was injected into the grafted tissue, labeled cells were found in several subcortical nuclei of the host, including the nucleus basalis of Meynert, ventral pallidum, thalamus, dorsal raphe, locus coeruleus, as well as the ipsilateral and contralateral neocortex. This study shows that grafts of dissociated neocortical tissue exhibit good survival and growth potential when implanted into infarcted neocortex and that several nerve fiber systems of the adult host have a regenerative capacity sufficient to innervate the grafted tissue.
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| 5. |
- Lindvall-Axelsson, Maria, et al.
(författare)
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Inhibition of cerebrospinal fluid formation by omeprazole
- 1992
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 115:3, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.
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| 6. |
- Cenci, M A, et al.
(författare)
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Characterization of in vivo noradrenaline release from superior cervical ganglia or fetal locus coeruleus transplanted to the subcortically deafferented hippocampus in the rat
- 1993
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 122:1, s. 73-87
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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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| 7. |
- Friedman, W J, et al.
(författare)
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Differential actions of neurotrophins in the locus coeruleus and basal forebrain.
- 1993
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 119:1, s. 72-8
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Tidskriftsartikel (refereegranskat)abstract
- The neurotrophin gene family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4/NT-5, supports the survival of distinct peripheral neurons, however, actions upon central neurons are relatively undefined. In this study we have compared different neurotrophins in the regulation of neuronal survival and function using dissociated embryonic cell cultures from two brain regions, the basal forebrain (BF) and locus coeruleus (LC). In the BF, NGF increased choline acetyl transferase (ChAT) activity, but did not influence cholinergic cell survival. In contrast to NGF, BDNF, NT-3, and the novel neurotrophin, NT-4, all increased ChAT activity and cholinergic cell survival. We also examined embryonic LC neurons in culture. LC neurons are unresponsive to NGF. In contrast, NT-3 and NT-4 elicited significant increases in survival of noradrenergic LC neurons, the first demonstration of trophic effects in this critical brain region. Identification of factors supporting coeruleal and basal forebrain neuronal survival may provide insight into mechanisms mediating degeneration of these disparate structures in clinical disorders.
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| 8. |
- Grabowski, Martin, et al.
(författare)
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Survival of fetal neocortical grafts implanted in brain infarcts of adult rats: the influence of postlesion time and age of donor tissue
- 1994
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 127:1, s. 126-136
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Tidskriftsartikel (refereegranskat)abstract
- We have previously found that fetal cortex taken from 16- to 18-day-old donors survives grafting to the infarcted cortex 5-7 days after middle cerebral artery occlusion. The present study was undertaken to examine the effect on graft survival of varying the age of the fetal donor tissue and the time between vessel occlusion and graft implantation. First, a cell suspension of neocortical tissue was grafted from fetuses aged 15, 17, or 20 gestational days to the infarcted cortex of hypertensive rats which had undergone arterial occlusion 5-7 days earlier. There were no significant differences in the mean size or general morphology assessed in Nissl- and acetylcholinesterase-stained sections between the groups. Second, neocortical tissue was grafted from fetuses aged 15 gestational days to the infarcted cortex at different times following arterial occlusion. When surgery was delayed until 5-7 days, 3 weeks, or 8 weeks postocclusion, graft survival was significantly better than when implanted 1 day postocclusion. Implantation after 3 weeks yielded grafts that also were significantly larger than those in rats grafted 5-7 days after cortical infarction. The results indicate that there is no crucial upper donor age limit for dissociated fetal neocortical grafts in terms of graft survival and volume. Furthermore, a delay between lesion and transplantation is desirable in this stroke model. The host brain environment seems to be most hospitable around 3 weeks after arterial occlusion.
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| 9. |
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| 10. |
- Kokaia, Merab, et al.
(författare)
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Seizure development and noradrenaline release in kindling epilepsy after noradrenergic reinnervation of the subcortically deafferented hippocampus by superior cervical ganglion or fetal locus coeruleus grafts
- 1994
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 130:2, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- Solid pieces of fetal locus coeruleus (LC) or superior cervical ganglion (SCG) were placed into a fimbria-fornix lesion cavity in 6-hydroxydopamine-treated, noradrenaline (NA)-denervated rats. Six to 8 months later, all animals were subjected to electrical kindling stimulations in the hippocampus until they had reached the fully kindled state. Nongrafted lesioned animals showed markedly increased kindling rate which was partly attenuated by LC but not SCG grafts. In both LC- and SCG-grafted animals, dopamine beta-hydroxylase immunocytochemistry demonstrated a high density of graft-derived noradrenergic fibers in the dorsal hippocampus, whereas reinnervation of the ventral hippocampus was much more sparse. Subregional distribution of these fibers within the hippocampus was different in the two grafted groups. Both grafts partly restored basal extracellular NA levels in the hippocampus and reacted to generalized seizures by a significant (two- to threefold) increase of NA release, as measured by intracerebral microdialysis. Our data indicate (i) that seizure activity can regulate transmitter release from noradrenergic neurons in both LC and SCG grafts, (ii) that only fetal LC grafts retard seizure development in kindling, and (iii) that the inability of SCG implants to influence kindling epileptogenesis could be due to a lack of synaptic contacts between the graft-derived ganglionic fibers and host hippocampal neurons.
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