Levetiracetam normalized E/I imbalance in the hippocampus after cortical stroke in aged mice
Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility. To investigate in vitro drug-induced seizure susceptibility (E/I imbalance) of GABAA receptor antagonist, gabazine (GZ), voltage-sensitive dye (VSD) imaging techniques were used in hippocampal brain slices. One month after PT stroke, in vivo aged PT stroke mice exhibited severe convulsive seizures (late-onset). in vitro GZ-induced E/I imbalance in hippocampus of aging mice increased compared to young adults. In addition, Anti-seizure medication (levetiracetam) normalized in vitro GZ-induced E/I imbalance in hippocampus of aging mice. These findings exhibited that GABAA receptor-mediated seizures susceptibility (E/I imbalance) in hippocampus after cortical PT stroke in aging mice, but not in young adults. Overall design: Photothrombosis (PT) model of cerebral ischemia was created by irradiating with LED light (wavelength; 565 nm, output; 200 mW) in a circle region with a diameter of 3.5 mm in the left parietal lobe region for 30 minutes after administration of rose bengal (35 mg/kg, i.p.) to C57BL/6N male mice (8-10 and 65-85 weeks old). One month after PT, mice were treated with anti-seizure medication, levetiracetam (LEV, free drinking, 5 mg/mL) for 2 weeks, and were withdrawn for 1 week after administration with LEV. An in vitro seizure susceptibility (E/I balance) was determined by voltage-sensitive dye (VSD) imaging techniques in hippocampal brain slices. By employing this approach, we investigated the in vitro GABAA receptor antagonist, gabazine (GZ).