Substantial evidence supports the notion that temporal lobe epilepsy is characterized by a transient, recurrent, self-sustained interruption of normal limbic functions, and a simultaneous hypersynchronous activation of a large population of neurons, most frequently in the hippocampus. Another line of research has provided evidence that fetal neurons may promote the reestablishment of severed connections in the mammalian brain and some of these new connections may help behavioral recovery of animals with experimental brain damage. A major goal of this proposal is to find suitable neuronal cell types of the fetal brain to prevent of suppress epileptic hypersynchronized activity. In addition, fetal hippocampal tissue with spontaneous epileptic activity will used to study the deteriorating effects of an """"""""implanted"""""""" epileptic focus and its surgical removal. The subcortically denervated hippocampus of the rat will be used as a chronic epilepsy model to study the effects of fetal grafts on the electrical activity and behavior of the host over several months. In the proposed experiments we will address the following specific questions: 1) Would transplantation of fetal epileptic tissue into the intact hippocampus induce interictal spikes and seizures in the host brain ? 2) Will removal of the epileptic """"""""focus"""""""" alleviate epileptic EEG and behavioral manifestations ? 3) Would some types of fetal cells (septal region, locus coerules, raphe region, substantia nigra, supramammillary region, n. reticularis thalami, cerebellum) be able to prevent the development of abnormal electrical patterns when transplanted into the epilepsy-prone hippocampus ? 4) Would fetal tissue of any kind be able to suppress epileptic activity several months after the establishment of abnormal electrical patterns ? Answers to these questions will clarify the mechanisms of epileptic synchronization, the development and spread of epileptic activity, and the suppressive action of various neurotransmitters on these processes under psychological conditions.
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