Chaihushugan decoction exerts antiepileptic effects by increasing hippocampal glutamate metabolism in pentylenetetrazole-kindled rats

Abstract

ObjectiveTo investigate the antiepileptic effects of Chaihushugan decoction (CHSGD) in rats with pentylenetetrazole (PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized underlying mechanism of seizure reduction. MethodsFifty Wistar rats were divided randomly into either control (n = 10) or experimental (n = 40) groups. Rats in the control group were administered physiological saline intraperitoneally. A sub-convulsive dose of PTZ (35 mg/kg) was administered intraperitoneally to rats in the experimental group to induce seizures. The fully PTZ-kindled rats were then randomly divided into five subgroups (n = 8 each) based on the following treatment categories: physiological saline, VPA (200 mg/kg), CHSGD (2.5 g/kg), CHSGD (5 g/kg), or CHSGD (10 g/kg), administered orally once per day, respectively. On day 28 following initiation of drug treatment, seizures were monitored. The rats were then sacrificed, and hippocampal dissections were performed for subsequent studies. ResultsCHSGD significantly prolonged the latency of myoclonic, clonic, and tonic seizures, while decreasing overall seizure rates in the kindled rats. The measured concentrations of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) and glutamate were significantly lower in the hippocampi of kindled rats in groups treated with CHSGD compared with those treated with PTZ alone. In addition, CHSGD was found to up-regulate both the expression of glutamate transporter-1 (GLT-1) protein and the activity of glutamine synthetase (GS) in the hippocampi of kindled rats. ConclusionThese results suggest that CHSGD has antiepileptic effects on PTZ-induced seizures. The results further suggest an increase in glutamate metabolism at the synaptic cleft is a putative underlying mechanism of seizure reduction.