1995 Fiscal Year Final Research Report Summary
The of the neurotrophic factor to the ischemic brain (in the aspect of the spatial learning ability)
| Project/Area Number |
06671396
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Ehime University School of Medicine |
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Principal Investigator |
KUMON Yoshiaki Ehime University, School of Medicine Assistant Professor, 医学部, 助教授 (80127894)
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| Co-Investigator(Kenkyū-buntansha) |
OHUE Shiroh Ehime University, School of Medicine Lecture, 医学部, 助手 (70213626)
KOHNO Kanehisa Ehime University, School of Medicine Lecture, 医学部, 講師 (60145076)
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| Project Period (FY) |
1994 – 1995
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| Keywords | focal cerebral ischemia / neurotrophic factor / Morris water maze test / ciliary neurotrophic factor / thalamus / intraventricular infusion |
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| Research Abstract |
The effect of repeated Morris water maze tests on the ability of place navigation was examined in rats with permanent unilateral occlusion of the middle cerebral artery, in relation to choline acetyltransferase (ChAT) immunoreactivity in the basal magnocellular nucleus of Meynert (NBM). MCA-occluded rats subjected to repeated water maze tests exhibited only transient disability of place-navigation. Despite the time dependent recovery of place-navigation activity in MCA-occluded rats, ChAT neurons in the NBM,which are considered to be involved in spatial learning ability, were fewer on the ischemic side than the non-ischemic side throughout the examination period. These findings suggest that early water maze training facilitates the functional restoration of MCA-occluded rats, and the recovery of place-navigation activity in the ischemic rats cannot necessarily be explained by a reduction in the ischemic injury of ChAT neurons in the NBM.
Ciliary neurotrophic factor (CNTF) has been shown to exhibit potent neurotrophic activity on peripheral and central neurons in vitro and in vivo. We infused CNTF continuously for 4 weeks into the lateral ventricle, starting just after permanent occlusion of the left middle cerebral artery (MCA) of stroke-prone spontaneous hypertensive rats. CNTF infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner in rats subjected to the Morris water maze task. Subsequent histological examinations showed that cortical infarction and retrograde degeneration of the ipsilateral thalamic neurons in ischerwc rats infused with CNTF were significantly less severe than those in ischemic rats infused with vehicle alone. These findings suggest that postischemic CNTF treatment prevents the occurrence of spatial learning disability in rats with permanent MCA occlusion, possibly by reducing neuronal damage within the cerebral cortex and secondary retrograde degeneration of the thalamus.
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