title: N-methyl-D-aspartic acid-induced and Ca-dependent neuronal swelling and its retardation by brain-derived neurotrophic factor in the epileptic hippocampus.
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) Ca2+-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 Ca2+ 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 Ca2+ from internal stores during the induction of epileptic swelling, and a neuroprotective role of BDNF on the NMDAR-induced swelling in the epileptic hippocampus.
authors.affiliation: Department of Physiology and Program in Neuroscience University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201, USA. misok001@umaryland.edu
authors.forename: M
authors.initials: M
authors.lastname: Isokawa
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D048429:Cell Size; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000166:cytology / Q000473:pathology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004827:Epilepsy / Q000473:pathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology*; D008027:Light; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D004533:Egtazic Acid; D016202:N-Methylaspartate; D019284:Thapsigargin; D000251:Adenosine Triphosphatases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium