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

• Published in: Neuroscience letters 2015-10, Vol.606, p.117-122
• Main Authors: Connell, Barry J., Gordon, John R., Saleh, Tarek M.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Brain - blood supply; Brain - drug effects; Brain - pathology; Brain Infarction - drug therapy; Brain Infarction - pathology; Brain Ischemia - drug therapy; Brain Ischemia - etiology; Brain Ischemia - immunology; Brain Ischemia - pathology; Chemokines, CXC - antagonists & inhibitors; Chemokines, CXC - immunology; Infarction, Middle Cerebral Artery - complications; Interleukin-8 - pharmacology; Interleukin-8 - therapeutic use; Male; Middle cerebral artery occlusion; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neutrophil; Peptide Fragments - pharmacology; Peptide Fragments - therapeutic use; Rats, Sprague-Dawley; Reperfusion injury; Stroke; Stroke - drug therapy; Stroke - etiology; Stroke - immunology; Stroke - pathology
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2015.08.041

•The ELR-CXC chemokine antagonist, CXCL8(3–72)K11R/G31P (G31P) is neuroprotective.•Protection was seen when G31P was administered 1 or 3h post-reperfusion. 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.