title: ELR-CXC chemokine antagonism is neuroprotective in a rat model of ischemic stroke.
abstract: 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 30 min followed by 5.5 h 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 (0.5 mg/kg) was administered 1 or 3 h 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.
authors: Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, P.E.I. C1A 4P3, Canada.
authors: Barry J
authors: BJ
authors: Connell
authors: Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors: John R
authors: JR
authors: Gordon
authors: Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, P.E.I. C1A 4P3, Canada. Electronic address: tsaleh@upei.ca.
authors: Tarek M
authors: TM
authors: Saleh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000276:immunology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D016209:Interleukin-8 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; C000604253:CXCL8(3-72)K11R,G31P, human; D019743:Chemokines, CXC; D016209:Interleukin-8; D018696:Neuroprotective Agents; D010446:Peptide Fragments
keywords: Anti-inflammatory; Middle cerebral artery occlusion; Neutrophil; Reperfusion injury; Stroke