Abstract

Dentate granule cell (DGC) swelling was studied by imaging changes in light transmittance from hippocampal slices in the rat pilocarpine model of epilepsy and human epileptic specimens. Brief bath-application of N-methyl- d-aspartic acid (NMDA) induced swelling in the control rat DGC (physiological swelling). Physiological swelling was short-lasting, and rapidly recovered upon removal of NMDA. In contrast, the swelling induced in the pilocarpine-treated rat hippocampus and human epileptic hippocampus (epileptic swelling) was long-lasting, and often recovered slowly over an hour. Both types of swelling were blocked by the NMDA receptor (NMDAR) antagonist, D-APV, suggesting that they shared the same induction mechanism. However, the swellings differed in their sensitivity to a calcium chelator, 1.2-bis(2-aminophenoxy)ethane- N, N, N, N-tetra-acetate (BAPTA), and an endoplasmic reticulum (ER) Ca 2+-ATPase inhibitor, thapsigargin (TG). BAPTA and TG affected only epileptic swelling, and physiological swelling was spared. This suggested that the NMDAR-induced epileptic swelling might involve an additional mechanism for its maintenance, likely recruiting ER Ca 2+ stores. Brain-derived neurotrophic factor (BDNF) slightly attenuated physiological swelling, and blocked epileptic swelling. The present study suggests a functional link between the activation of NMDAR and a release of Ca 2+ from internal stores during the induction of epileptic swelling, and a neuroprotective role of BDNF on the NMDAR-induced swelling in the epileptic hippocampus.

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