ABSTRACT NUMBER: ESOC2026A1894 TRANSLATIONAL CHRONIC DEFICITS AND TISSUE CHANGES AFTER LARGE STROKE, IN YOUNG- AND OLD-AGED MICE

Abstract Background and aims Ischemic stroke causes significant long-term residual deficits that are poorly modelled and understood. Here, we build on our previous concept of “chronic mouse stroke model” to study 6-months´ clinical and tissue changes in young and old mice. Methods Adult male C57BL/6N young (n=31, 3 months old) and old (n= 30, 14 months old) mice were subjected to 1 hour transient middle cerebral artery occlusion with filament (fMCAo), were optimally supported with the “mouse Stroke Unit” protocol to increase survival for long-term studies, and were followed behaviorally (the open-field, tail suspension, cylinder, Corner and the horizontal ladder-rung test) and clinically (temperature, body weight, detailed neurological status) up to 6 months. At 6 months, brains and spinal cords were cryosectioned and studied for local and remote atrophy and cellular changes. Results Old mice had significantly higher acute mortality versus young, primarily due to edema-related herniation. Survivors exhibited prolonged (>1 month) and age-dependent weight loss (p<0.05). Both age groups developed severe focal neurological deficits with partial spontaneous recovery but persistent sensorimotor impairments up to 6 months. Ιpsilesional hemispheric atrophy (approximately 30% in both groups) was accompanied by ventricular enlargement and remote atrophy of sensory cortex, corpus callosum and thalamus, associated with ultra-chronic, region- and age-dependent astrocytic and microglial activation in brain. Spinal cord architecture showed preserved neuronal populations with affected contralateral corticospinal tracts and corresponding chronic residual microglial activation. Conclusions Mice can translationally model core long-term ischemic stroke parameters, revealing multiple chronic targets for drug discovery and treatment in stroke. Conflict of interest CP, IM and AL were supported by Unipharma S.A. with Research Grants. NK: nothing to disclose, APav: nothing to disclose, NZ: nothing to disclose, MG: nothing to disclose, ES-P: nothing to disclose, CPet: nothing to disclose, NP:nothing to disclose, AKot: nothing to disclose, AC: nothing to disclose, AKok: nothing to disclose