Experimental study to facilitate the repaair of brain injury by artificial modification of cellular function and brain transplantation.

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The repair process of injury after focal ischemia was studied with special reference on the proliferation of glial population. Therapeutic measure was then searched for to ameliorate or repair the ischemic brain injury.1. The dynamic profile of proliferation of glial cells was studied 1 to 7 days after focal cerebral ischemia in gerbils. The results indicated that the astrocytes proliferated actively at the periphery of infarcted brain during days 1 to 5 postinfarction with most active DNA synthesis at day 3. Additionally, those regions were infiltrated with large number of polymorphonuclear cells and macrophages. The latter type of cells seems especially important since they were positive for interleukin 1 (IL-1).2. Effect of preceding small stab wound on the evolution of hippocampal neuronal death was studied in gerbils. The results indicated that a certain kind of protective mechanism was induced by this type of minor injury to save hippocampal pyramidal neurons from delayed death after transient ischemia. The effect was most impressive when the hippocampus was stabbed 24 hours before ischemic insult.3. The growth and differentiation of transplanted neonatal subependymal cells was studied after transplantation into adult hippocampus. Those cells proliferated for a few weeks in a limited fashion, and differentiated to glial cells but not neurons. We further studied transplantation of fetal subependymal cells, a substantial number of which differentiated to neurons.4. The neonatal hippocampal tissue was transplanted into the hippocampus of adult gerbils at 1 to 4 weeks after transient forebrain ischemia. The results demonstrated that the infarcted hippocampus, especially 1 week after transient ischemia, was feasible for survival of transplanted neural tissue.