The Role of Neural Stem Cell and Neural Plasticity in the Model of Epilepsy

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To investigate the proliferation and migration of neural stem cells (NSC) as well as neural plastic changes in epileptic brain, spaciotemporal expressions of immunoreactive bromodeoxyuridine (BrdU) and highly polysialylated neural cell adhesion molecule (PSA-NCAM) were examined in amygdala kindling of rat.Amygdaloid kindling in partial seizure (PS) was effective in proliferation of NSC detected with BrdU-labeling in subventricular zone (SVZ), but not in dentate gyrus (DG). In SVZ, however, the BrdU-labeling cells decreased at 3 times generalized seizures (3 GS).The neural migration and synaptic remodeling detected with PSA-NCAM staining occurred in DG of hippocampus, subventricular zone and pyriform cortex with amygdaloid kindling in GS but not in PS. The number of PSA-NCAM positive cells in bilateral DG increased significantly at GS. Although total positive cell number was not significantly different between 3 GS and 30 times GS (30 GS) groups, a greater number of positive cells was located in the outer granule cell layer, and the immunopositive dendrite greatly extended to the molecular layer in 30 GS group. The number of PSA-NCAM positive cells increased 4 times in the bilateral SVZ at 3 GS, with a further increase at 30 GS.These facts indicate that proliferation of NSC increased with PS and decreased with severer seizures of GS in SVZ, and that such a proliferation did not occur in DG with PS or GS. Thus, the proliferation of NSC was spacially and temporally different between brain regions depending on different kindling stages. The increased migration of newly generated cells as well as plastic change of originally-existed neural cells may occur in response to the recurrent GS, which may contribute to abnormal reconstruction of synaptic network in hippocampus and epileptogenisity in kindling.