title: The anti-seizure drugs vinpocetine and carbamazepine, but not valproic acid, reduce inflammatory IL-1β and TNF-α expression in rat hippocampus.
abstract: In the present study, the effects of the two classical anti-epileptic drugs, carbamazepine and valproic acid, and the non-classical anti-seizure drug vinpocetine were investigated on the expression of the pro-inflammatory cytokines IL-1β and TNF-α in the hippocampus of rats by PCR or western blot after the administration of one or seven doses. Next, the effects of the anti-seizure drugs were investigated on the rise in cytokine expression induced by lipopolysaccharides (LPS) inoculation in vivo. To validate our methods, the changes induced by the pro-convulsive agents 4-aminopyridine, pentylenetetrazole and pilocarpine were also tested. Finally, the effect of the anti-seizure drugs on seizures and on the concomitant rise in pro-inflammatory cytokine expression induced by 4-aminopyridine was explored. Results show that vinpocetine and carbamazepine reduced the expression of IL-1β and TNF-α from basal conditions, and the increase in both pro-inflammatory cytokines induced by LPS. In contrast, valproic acid failed to reduce both the expression of the cytokines from basal conditions and the rise in IL-1β and TNF-α expression induced by LPS. Tonic-clonic seizures induced either by 4-aminopyridine, pentylenetetrazole or pilocarpine increased the expression of IL-1β and TNF-α markedly. 4-aminopyridine-induced changes were reduced by all the tested anti-seizure drugs, although valproic acid was less effective. We conclude that the anti-seizure drugs, vinpocetine and carbamazepine, whose mechanisms of action involve a decrease in ion channels permeability, also reduce cerebral inflammation. The mechanism of action of anti-seizure drugs like vinpocetine and carbamazepine involves a decrease in Na(+) channels permeability. We here propose that this mechanism of action also involves a decrease in cerebral inflammation.
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF, México.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Gómez
authors.forename: Rudolf M
authors.initials: RM
authors.lastname: Buijs
authors.forename: María
authors.initials: M
authors.lastname: Sitges
mesh_terms: D015761:4-Aminopyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002220:Carbamazepine / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014635:Valproic Acid / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D018076:DNA, Complementary; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014748:Vinca Alkaloids; D002220:Carbamazepine; C013983:vinpocetine; D014635:Valproic Acid; D015761:4-Aminopyridine
keywords: 4-aminopyridine; Anti-epileptic drugs; brain inflammation; epilepsy; lipopolysaccharides; sodium channels