Neuroprotective actions of pyridoxine.
Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5 alpha-pregnan 3 alpha-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background. Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D. In hippocampal cells, domoic acid-induced increases in glutamate and calcium influx were significantly decreased by pyridoxal phosphate or nimodipine. Similarly in neuroblastoma-glioma hybrid cells (NG 108/15), pyridoxine attenuated domoic acid-induced increases in glutamate, influx of extracellular calcium, and enhanced induction of oncoproteins regardless of whether cells were undifferentiated, differentiated or de-differentiated. Pyridoxine has anti-seizure and neuroprotective actions mediated through mechanisms similar to those targeted by current therapeutic strategies.
Dakshinamurti
Krishnamurti
K
Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada MB R3E 0W3. dakshin@cc.umanitoba.ca
Sharma
S K
SK
Geiger
Jonathan D
JD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D011736:Pyridoxine / Q000494:pharmacology*
D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D011736:Pyridoxine; C012301:domoic acid; D007608:Kainic Acid; D002118:Calcium