Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke.

• Acute ischemic stroke impaired the white matter integrity of pig internal capsules. • Increased hemispheric swelling and hemorrhage resulted in notable midline shift. • Pig neutrophil-to-lymphocyte levels replicate patient outcomes at acute timepoints. • Evidence of post-stroke depression was observed via reduced exploratory behavior. • Pigs replicated patient deficits through gait impairments in the hemiplegic limb. The acute stroke phase is a critical time frame used to evaluate stroke severity, therapeutic options, and prognosis while also serving as a major tool for the development of diagnostics. To further understand stroke pathophysiology and to enhance the development of treatments, our group developed a translational pig ischemic stroke model. In this study, the evolution of acute ischemic tissue damage, immune responses, and functional deficits were further characterized. Stroke was induced by middle cerebral artery occlusion in Landrace pigs. At 24 h post-stroke, magnetic resonance imaging revealed a decrease in ipsilateral diffusivity, an increase in hemispheric swelling resulting in notable midline shift, and intracerebral hemorrhage. Stroke negatively impacted white matter integrity with decreased fractional anisotropy values in the internal capsule. Like patients, pigs showed a reduction in circulating lymphocytes and a surge in neutrophils and band cells. Functional responses corresponded with structural changes through reductions in open field exploration and impairments in spatiotemporal gait parameters. Characterization of acute ischemic stroke in pigs provided important insights into tissue and functional-level assessments that could be used to identify potential biomarkers and improve preclinical testing of novel therapeutics. [ABSTRACT FROM AUTHOR]