ELR-CXC chemokine antagonism is neuroprotective in a rat model of ischemic stroke

Publication date: 8 October 2015 Source:Neuroscience Letters, Volume 606 Author(s): Barry J. Connell, John R. Gordon, Tarek M. Saleh Inflammation-related cerebral damage mediated by infiltrating neutrophils following reperfusion plays a role in reperfusion-induced brain damage subsequent to a stroke event. The ELR-CXC family of chemokines are CXCR1 and CXCR2 agonists that are known to drive neutrophil migration and activation. The present study demonstrated the benefit of anti-inflammatory therapy in the treatment of ischemic stroke with the administration of the competitive ELR-CXC chemokine antagonist, CXCL8(3–72)K11R/G31P (G31P). Male Sprague-Dawley rats were anaesthetized, and the middle cerebral artery (MCA) was occluded for 30min followed by 5.5h of reperfusion. Pretreatment with G31P resulted in a significant, dose-dependent (approximately 61–72%) decrease in infarct volumes compared to vehicle-treated animals, but neuroprotection was also observed when G31P (0.5mg/kg) was administered 1 or 3h following the start of reperfusion. The neuroprotection observed following the administration of this competitive CXCR1/CXCR2 antagonist may present therapeutic opportunities for addressing reperfusion-induced inflammatory damage in patients presenting with transient ischemic episodes.
Source: Neuroscience Letters - Category: Neuroscience Source Type: research