Pinellia Total Alkaloids Modulate the GABAergic System in Hippocampal Formation on Pilocarpine-Induced Epileptic Rats

Objective: To investigate the neuromodulatory effect of pinellia total alkaloids(PTA) on the gamma-aminobutyric acidergic(GABAergic) system in epileptic rats, and preliminarily evaluate the anti-epileptic effect of PTA. Methods: Ninety-one male Sprague-Dawley rats were randomized to a control group(n=17) or an epileptic group(n=74) using computer-generated random numbers. Status epilepticus(SE) was induced with pilocarpine in the epileptic group. Epileptic rats that survived SE were randomly divided into 4 groups, namely an epilepsy group(n=13), a topiramate(TPM, 60 mg/kg) group(n=12), a high-dose PTA(800 mg/kg) group(n=12), and a low-dose PTA(400 mg/kg) group(n=10). Treatments were given intragastrically once daily for 14 days. The control group and epilepsy group received normal saline. Spontaneous recurrent seizures(SRSs) were monitored 8-h daily for 7 days after treatment. Then, the hippocampal formation tissues were collected. GABA level was measured using enzyme-linked immunosorbent assay. Protein and mRNA expression levels of glutamate decarboxylase 65(GAD65), GABA transporter-1(GAT-1), GABA transaminase(GABA-T), and GABAA receptor(GABAAR) α4, α5, γ2 and δ subunits were measured using Western-blotting analysis and quantitative polymerase chain reaction. Results: PTA lowered the incidence and frequency of SRS(both doses vs. the TPM group, P0.05). Compared with the epilepsy group, PTA increased the levels of GABA(both doses P0.01) and GAD65(mRNA, 800 mg/kg, P0.01), and suppressed the levels of GAT-1(mRNA, 800 mg/kg, P0.01; 400 mg/kg, P0.05), GABA-T(mRNA, both doses P0.01), and GABAAR δ subunit(protein, 800 mg/kg, P0.05) and γ2 subunit(protein, both doses P0.01). PTA upregulated the low-expressed mRNA levels of GABAAR α5 subunit(400 mg/kg, P0.01), δ subunit(800 mg/kg, P0.05), and γ2 subunit(400 mg/kg, P0.05). Conclusions: PTA regulated the GABAergic system through modulating GABA levels and the expression levels of GAD65, GAT-1, GABA-T, and GABAAR α4, α5, γ2 and δ subunits. PTA may exert antiepileptic effects on the pilocarpine-induced epilepsy model.     

Effects of Low‐Frequency Hippocampal Stimulation on Gamma‐Amino Butyric Acid Type B Receptor Expression in Pharmacoresistant Amygdaloid Kindling Epileptic Rats

Objective: To observe the effect of low‐frequency hippocampal stimulation on gamma‐amino butyric acid type B (GABA‐B) receptor expression in hippocampus pharmacoresistant epileptic rats. Materials and Methods: Sixteen pharmacoresistant epileptic rats were selected by testing their seizure response to phenytoin and phenobarbital, and they were randomly divided into a pharmacoresistant control group (PRC group, eight rats) and a pharmacoresistant stimulation group (PRS group, eight rats). Another 16 pharmacosensitive epileptic rats were served as control, also divided randomly into a pharmacosensitive control group (PSC group) and a pharmacosensitive stimulation group (PSS group). A stimulation electrode was implanted into the rats' hippocampus in the four groups. Low‐frequency hippocampal stimulation was administered twice per day for two weeks. Following these weeks of stimulation, GABA‐B receptor‐positive neurons were counted and the gray values of GABA‐B receptor expression in the rats' hippocampal tissues were measured. Results: The amygdale stimulus‐induced epileptic seizures were decreased significantly in the PRS group compared with the PRC group. The parameters of the amygdale after discharge also were improved after hippocampal stimulation. Simultaneously, the GABA‐B receptor‐positive neurons increased and the GABA‐B expression gray values decreased markedly in the PRS group compared with the PRC group. The same phenomenon also was observed between the PSS group and the PSC group. However, no significant difference was found in the GABA‐B receptor‐positive neurons and the gray values of GABA‐B between the PRS group and the PSC group. Conclusions: The low‐frequency hippocampal stimulation may inhibit the amygdale stimulus‐induced epileptic seizures and the after discharges. The antiepileptic effects of the hippocampal stimulation may be achieved partly by increasing the expression of the GABA‐B receptor.     

Seizure management at Auckland City Hospital Emergency Department between July and December 2009: time for a change?

Aims: To assess the management of epileptic seizures and status epilepticus in adult patients at Auckland City Hospital emergency department. This information will form the basis of future seizure management protocols and further research on the management of status epilepticus. Methods: The prehospital and acute hospital management of all adult seizure patients seen between 1 July 2009 and 31 December 2009 was reviewed with respect to seizure type, presence of first seizure, pre‐existing epilepsy diagnosis and disposition from the emergency department. Results: Two hundred and fifty‐five seizure events were identified in 227 patients. Nineteen patients presented twice during the study period and three patients presented three or more times. Generalised seizures were much more common than focal seizures. There were 75 presentations with first seizure (29.4%). Thirty‐seven patients (49.3%) with a first seizure received treatment with an anti‐epileptic drug. Status epilepticus occurred on 12 occasions (4.7%) with only three patients receiving lorazepam as treatment. The majority of seizure patients were managed by emergency department staff (58.4%) while general medicine (17.6%) and neurology (11.8%) teams managed fewer patients. Phenytoin was used in 56 patients (22%) with the majority (n= 43) receiving intravenous phenytoin. Many of the patients who received intravenous phenytoin were not subsequently discharged on that medication (46%). Conclusions: More patients than would be expected received treatment after their first seizure. Phenytoin was a widely used anti‐epileptic drug. There was a wide variability in the management of status epilepticus, and intravenous lorazepam was underutilised.