APOPTOSIS OF HIPPOCAMPAL-NEURONS AFTER AMYGDALA-KINDLED SEIZURES

Seizure-induced neuronal damage may involve both excitotoxic and apopt otic (programmed cell death) mechanisms. In the present study, we used an amygdala kindled seizure model to study whether apoptotic cell dea th occurs. To evaluate apoptosis, we counted the numbers of cells that had DNA fragments labeled at the 3' end with digoxigenin using termin al transferase (ApopTag, Oncor). Additionally, the expression of Bar a nd Bcl-2, two genes associated with apoptotic cell death, was also mea sured following kindled seizures. We found that the number of ApopTag- positive cells in the hippocampus increased 30.4% after one kindled se izure and 82.5% after 20 seizures compared to sham controls. The ApopT ag-labeled cells could be mainly interneurons of the hippocampal forma tion, although additional studies are required. Preferential vulnerabi lity of inhibitory interneurons is consistent with previous studies on seizure-induced cell, loss. These results, coupled with our findings that the ratio of Bax/Bcl-2 expression is increased in the hippocampus by seizures, suggest that apoptosis of hippocampal interneurons may l ead to dysinhibition in the hippocampus and increased seizure suscepti bility. (C) 1998 Elsevier Science B.V.