Photothrombotic Cerebral Stroke as a Model of Post-Stroke Seizures/Epilepsy 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 and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke 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 week after the PT stroke, MRI images were taken to observe the state of cerebral infarction, and chronic EEG screw electrodes were placed in the frontal lobe/parietal lobe. To investigate GABAA receptor-related convulsive/non-convlsive seizures after PT stroke, low-doses (20~30 mg/kg, i.p.) pentylenetetrazol (PTZ), GABAA receptor antagonist, was injected, and video-EEG monitoring was performed to detect seizures. One month after PT, mice were treated with anti-seizure medication, levetiracetam (LEV, free drinking, 5 mg/mL) for 2 weeks, and were withdrawal for 1 week after administration with LEV.