Rodiyah Temi Ajala-Jabar

Introduction. Post-stroke epilepsy (PSE) is the re-occurrence of two or more unprovoked seizures more than twenty-four hours apart, and at least one week after a patient experiences stroke.^{1, 2} PSE accounts for 10% of all epilepsy cases, diagnosed in up to 22% of patients after stroke and accounts for up to 55% of epilepsy diagnoses among geriatric patients making it the most common cause of epilepsy for this population.^{1, 3} With world population aging and increased prevalence of post-stroke survivors, the number of patients with PSE is expected to increase.³ This report aims to elucidate epileptogenesis of PSE to reliably prognosticate stroke patients and identify possible disease-modifying therapies that can be studied further in human clinical trials as current pharmacologic therapies offers only symptomatic control of epilepsy using anti-epileptic drugs (AEDs) such as levetiracetam and statins.^{1, 4}  Methods. Three stroke-causing models were utilized to induce seizures and epilepsy in rats. Two models employed combination of middle cerebral, common carotid and vertebral arteries surgical occlusion permanently or transiently while the third model employed less invasive photothrombosis.^5-8 Video-monitoring, in-vivo and ex-vivo electroencephalography (EEG), MRI, qRT-PCR, microarray analysis, immunochemical-staining and western-blotting were used to detect and monitor pro-inflammatory cytokines (PICs), GABA, GABA receptor and transporter subunits and K+ receptor subunits expression within the rats’ brains.^5-8 In human studies, stroke patients’ blood was retrospectively qRT-PCR analyzed for PICs IL-6 and IL-1β to predict seizure re-occurrence.^{9, 10}  Results. Aged rats showed low incidence of PSE (3-10%) due to high and early mortality caused by severe neuronal damage from experimental procedures making PSE epileptogenesis study difficult.⁵ Inflammation preceded GABA-related changes and epileptiform discharges, evidenced by MRI scans showing edema and increased intracranial pressures in stroke-induced rats compared to controls.^{6, 8} Administration of miR-155 inhibitor prior to stroke-induction maintained GABA inhibitory function.⁸ IL-6 and IL-1beta blood levels in stroke patients independently predicted seizure re-occurrence with moderate sensitivity (68.57% and 70.09%) and specificity (75% and 87.02%).^{9, 10}  Conclusions. These studies show that intrinsic neuronal membrane changes caused by reduced expression of GABA receptor and K+ channel subunits and increased expression of GABA transporter subunits.^6-8 These changes contribute to hyperexcitability from lower GABA levels thus they reduce GABA-mediated inhibition and seizure-generating thresholds. Subsequently, when these expression levels are left uncorrected, long-term susceptibility to PSE results.^6-8 Human clinical trials are needed to determine if miR-155 inhibitor can be employed prophylactically in high-risk stroke patients to attenuate inflammation and prevent PSE epileptogenesis. Finally, by measuring blood PICs as biomarkers, PSE can be prognosticated early in stroke patients.^{9, 10}

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