Abstract 122: Selective Intra-Arterial Cooling (SI-AC) Improve Recovery in a Nonhuman Primate Model of Ischemic Stroke

Abstract

Background and Purpose: Recent findings from our group prove that selective intra-arterial cooling (SI-AC) treatment leads to prominent and persistent functional improvements after stroke in both rodents and non-human primate (NHPs) stroke models. In this study, neuro-protective potentials of SI-AC treatment were further explored at brain network and histopathological levels in preclinical higher-order brains. Methods: Cerebral ischemia/reperfusion was induced by thrombus and thrombolysis (t-PA) in adult rhesus monkeys (n=10). SI-AC treatment was randomly given to 5 models. Conventional MRI and diffusion tensor imaging scans were performed 4 h, 7 and 30 days post focal ischemia. Effects on functional recovery were also assessed through longitudinal neurologic scores and behavior tests. Animals were euthanized after the final scan for histological analysis. Results: SI-AC treatment led to a higher rate of infarct reversal, significantly mitigated neurologic deficits, and more preserved dexterity when compared with those only receiving t-PA during a 30-day observation period. More fiber numbers, a higher FA values based on DTI analysis, and a higher integrity of white matter based on immunochemistry in ipsilateral side were observed in models receiving t-PA plus SI-AC during the same observation period. Histological findings, consistent with MRI images in the infarct size and reversal, indicated that myelin damage, spheroids, and spongiosis were significantly improved in models receiving SI-AC treatment than those with t-PA alone treatment. Conclusions: Our findings further supported that SI-AC as an adjunctive treatment could significantly improve neural tissue and functional preservation in a large animal model, suggesting its potential application in ischemic stroke treatments.