Transient protective effect of B-vitamins in experimental epilepsy in the mouse brain.
The regulation of programmed cell death in the nervous system of vertebrates is a complex mechanism aimed to remove superfluous or damaged cells. Epileptic seizures can lead to an activation of pathways resulting in neuronal cell death. B-vitamins might have a neuroprotective potential reducing cell death following appropriate stimulation. Here, the role of the B-vitamins B(1) (thiamine), B(6) (pyridoxine), and B(12) (cobalamine) was investigated in a mouse model of experimental epilepsy induced by kainate. B-vitamin pre-treated animals showed a significantly reduced epileptic score during the first 15 min after kainate injection. The molecular response to kainate showed a bi-phased time course with early induction of Bcl-2 expression within 12 h and a second induction after 7 days of kainate exposure. B-vitamin pre-treatment resulted in significant higher Bcl-2 expression in control animals (no kainate) and at 12 h within the early phase. Bcl-2 expression was not affected by B-vitamins within the second phase. BAX expression was not significantly influenced during the whole experiment. Three days after kainate stimulation, the number of TdT-mediated dUTP-biotin nick end labeling-positive cells in the hippocampal region was lower in B-vitamin-treated animals. Therefore, B-vitamin pre-treatment may attenuate the response to epileptic stimulation.
Department of Physiology and Pathophysiology, University of Heidelberg Medical School, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany.
Tamer
T
Rabie
Wolfgang
W
Mühlhofer
Thomas
T
Bruckner
Anna
A
Schwab
Alexander T
AT
Bauer
Manfred
M
Zimmermann
Dieter
D
Bonke
Hugo H
HH
Marti
Johannes
J
Schenkel
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D016923:Cell Death; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D014803:Vitamin B Complex; D007608:Kainic Acid