2005 Fiscal Year Final Research Report Summary
Neuronal Regeneration Therapy for Cerebral Ischemia
| Project/Area Number |
16390404
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KAWAHARA Nobutaka The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (60214673)
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| Project Period (FY) |
2004 – 2005
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| Keywords | regenerative medicine / neuroscience / neurological diseases / cerebral ischemia |
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| Research Abstract |
In this research project, the investigators initially tried to regenerate striatal neurons in focal ischemia in rats. Since no significant number of neurons could be regenerated, we changed the model to global ischemia in which consistent striatal neuronal death can be quantified. In this model, more than 95% of neurons located in the dorsolateral part of the striatum are lost. Six weeks after ischemia, no significant neuronal regeneration was observed in untreated animals. Since the number of proliferating progenitor at the subventircular zone peaked at 7 day, we treated the rats with growth factors starting form Day 2 to 9 to cover this period. Consequently, the number of neurons increased by 15 % at 6 week, which is significant at p<0.05. These neurons incorporated BrdU, a marker of proliferating cells, and exhibit mature neuronal phenotype. In particular, these neurons expressed the marker for GABAergic interneurons, but not DARPP-32, a marker for projection neurons.
We also started to establish a model of cerebral ischemia in non-human primates (Macaca fascicularis). Although we first tried to make focal ischemia by occluding the middle cerebral artery by endvascular technique, we could not obtain consistent lesion in the corresponding hemisphere. We, therefore, changed the model to global ischemia. In this model, great vessels to the brain are occluded by endvascular balloon, which led to disappearance of electroencephalogram within 1 minute. We first initially occlude for 20 minutes, according to the literature, which however was too severe to obtain long-term survival. We gradually shortened the time, up to 8 minute. This time period appeared to be suitable at the moment. The establishment of primate model of global ischemia for assessment of neuronal regeneration seems to be an important step toward clinical application
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