title: Chaihushugan decoction exerts antiepileptic effects by increasing hippocampal glutamate metabolism in pentylenetetrazole-kindled rats.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Fifty 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 subconvulsive 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.
  
  
  RESULTS
  CHSGD 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-diazo-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.
  
  
  CONCLUSIONS
  These 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.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Changjun
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D010433:Pentylenetetrazole / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D004365:Drugs, Chinese Herbal; D005971:Glutamates; D010433:Pentylenetetrazole