Baicalein administration protects against pentylenetetrazole-induced chronic epilepsy in rats

Purpose: To investigate the protective effect of baicalein against chronic seizures in pentylenetetrazole induced epilepsy in a rat model. Methods: A rat model of chronic epilepsy was prepared by administration of pentylenetetrazole at a dose of 35 mg/kg to Sprague-Dawley rats. The animals were divided into 6 groups (5 rats/group): normal control, model (untreated epilepsy) and four treatment groups that received separately, intraperitoneal injection of 20, 30, 40 and 50 mg/kg baicalein, respectively, on alternate days for 30 days. On each day following baicalein treatment, behavioural alterations in the rats were assessed. Results: Analyses of behavioural changes revealed significant (p < 0.05) decrease in pentylenetetrazole-induced convulsions by baicalein treatment at a dose of 50 mg/kg. Immunohistochemical studies revealed that treatment with baicalein caused significant (p < 0.05) dose-dependent reductions in the levels of inducible nitric oxide synthase (iNOS). Baicalein treatment inhibited alterations in cell morphology, and also inhibited pentylenetetrazole-induced increase in the proportion of glial fibrillary acidic protein (GFAP)-positive cells in a dose-dependent manner (p < 0.05). Real-time polymerase chain reaction (RT-PCR) analysis showed that baicalein significantly inhibited the expression of mRNA of NR1 subunit N methyl D aspartic acid (NMDA) receptor, without any effect on the expression of the NR2b (N-methyl D-aspartate receptor subtype 2B) subunit mRNA (p < 0.05). Conclusion: These results indicate that baicalein inhibits pentylenetetrazole-induced chronic seizures in rats via reduction in astrocytes, inhibition of neuronal death and reduction of NR1 mRNA expression. Thus, baicalein has a potential for development into a new drug for the treatment of chronic epilepsy.