Modulation Effects Of Alpha-Asarone On The Gaba Homeostasis In The Lithium-Pilocarpine Model Of Temporal Lobe Epilepsy

In our previous study, we have proved that cc-asarone had an obviously antiepileptic effect on various experimental models of epilepsy, but the putative mechanism of action has remained elusive. The objective of present study was to investigate the modulation effects of alpha-asarone on gamma-aminobutyric Acid (GABA) homeostasis in the rat lithium-pilocarpine model of TLE. Adult Wistar rats were subjected to Status Epilepticus (SE) induced by lithium-pilocarpine. Rats were randomized into three groups, LI-PILO group (sham-treated group), LI-PILO+a-asarone group (a-asarone treated group) and normal control group. aAsarone treated group were administered orally with a-asarone (200 mg kg day'), twice daily, for 7 days. Rats were sacrificed 12, 24, 48, 72 h and 7 day after SE. Changes in GABA level and GABA transaminase (GABA-T) activity were compared. The expression of glutamic acid decarboxylase 67 (GAD67) and GABAA receptor were measured in brain sections from different groups of experimental rats by Tiger920 image analysis system. The hippocampal GABA levels and GAD67 protein expression in the sham-treated group significantly decreased 12-24 h after SE (p<0.05). Then it slowly increased at 72 h after SE. An extremely higher activity of GABA-T was found in sham-treated group than normal control group at various time-points after SE (p<0.05). GABAAR-mRNA expression was significantly lower in sham-treated group than normal control group 12-24 h after SE. The expression peak of GABAAR-mRNA appeared 48-72 h after SE in sham-treated group. The hippocampal GABA levels, GAD67 and GABAAR-mRNA expression in a-asarone treated group were significantly higher at various time-points after SE. alpha-asarone significantly decreased activity of GABA-T at various time-points after SE and a stronger inhibitory effect of alpha-asarone on GABA-T activity was found in hippocampus than frontal lobe. This study suggests that GABAergic modulation is involved in the antiepileptic action of cc-asarone.