TRANSPLANT OF GABAERGIC NEURONS INTO THE SUBSTANTIA NIGRA OF KINDLED RATS

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This project will investigate the effect of transplanting neuronal suspensions from the cerebellum of 16 day old rat embryos into the substantia nigra of adult kindled rats. The hypothesis is that the substantia nigra is involved in the control of spread of seizures and the addition of gamma amino butyric acid (GABA)ergic neurons to the nigra will prevent the seizures. GABAergic neurons are obtained by gentle trypsinization of the cerebellum of 16 days old embryos. These cells are then transplanted into the substantia nigra using a Harvard pump. The origin of the cells will be determined by staining with the glutamate decarboxylase (GAD) antibody as well as cerebellum specific antibodies. Our most recent results show at a light microscopic level a fine network of cells at the area of transplant in the nigra. These cells are elongated in shape with extensive processes. They have failed to stain with GAD antibody, but other GABAergic neurons in the area have not stained either. We are currently investigating the reasons behind this. Preliminary work has shown that kindling disappears for 2 weeks after transplant but then returns. The reasons for these findings are being investigated. The substantia nigra has been shown to be a controlling point of seizure spread by numerous investigators. The current study will attempt to demonstrate whether transplants of GABAergic neurons from rat embryo cerebellum will block the spread of seizures. The results of these studies were largely negative. The reasons for these findings could be multiple, among them the failure to be able to grow the GABAergic neurons and to form synapses. The conclusions of this study are that further basic knowledge of the neurobiology of brain transplants is needed before their usefulness in neurologic diseases can be evaluated.