Abstract 64: Perlecan LG3 is Neuroprotective When Administered Intra-arterially After Experimental Ischemic Stroke

Abstract

Despite recent advances in stroke therapy, stroke remains a leading cause of morbidity and mortality. We have previously demonstrated the therapeutic potential of exploiting the brain’s endogenous protection and repair processes following stroke. Specifically, we reported that the LG3 protein fragment of the heparan sulfate proteoglycan perlecan is neuroprotective and proangiogenic in vitro. We now hypothesize that LG3 could be therapeutic in experimental stroke. However, as previous in vivo LG3 studies suggest that it may not readily target stroke-affected brain upon systemic administration, we administered LG3 in a super selective intra-arterial (IA) model (into the ipsilateral common carotid artery) following transient (1 hour) middle cerebral artery occlusion in 3 month old male mice. Upon reperfusion the mice received LG3 or vehicle controls via IP (5 mg/kg) or IA (0.15 mg/kg) administration. No differences in vital signs were noted between the treatment groups. We observed that all LG3 treated mice, regardless of route of administration, had a smaller infarct compared to controls on post-stroke day 3. Importantly, those mice that received IA LG3 had much smaller strokes and performed significantly better in forced movement and in free movement settings than all other treatment conditions. Our results demonstrate that acute LG3 administration is beneficial after experimental ischemic stroke, IA LG3 is safe and much more effective than IP, and support further investigation of LG3 as a novel acute stroke therapy.