CXCR4 Antagonist AMD3100 Protects Blood–Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice
Top Cited Papers
- 1 January 2013
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 44 (1), 190-197
- https://doi.org/10.1161/strokeaha.112.670299
Abstract
Inflammatory response plays a critical role in propagating tissue damage after focal cerebral ischemia. CXCL12 is a key chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the pharmacological antagonist of CXCR4, AMD3100, to investigate the function of CXCL12/CXCR4 in regulating inflammatory response during acute ischemia. Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain water content, infarct volume, neurological score, and myeloperoxidase (MPO) expression and activity were examined at 24, 48, and 72 hours after MCAO. Proinflammatory cytokine RNA and protein levels in brain tissue were measured by RT-PCR and enzyme linked immunosorbent assay. Neurological score was greatly improved in AMD3100-treated mice compared with the control mice 3 days after MCAO ( P P P <0.05). CXCR4 antagonist AMD3100 significantly suppressed inflammatory response and reduced blood–brain barrier disruption after MCAO. AMD3100 attenuated ischemia-induced acute inflammation by suppressing leukocyte migration and infiltration, in addition to reducing proinflammatory cytokine expression in the ischemic region.Keywords
This publication has 32 references indexed in Scilit:
- Dual stem cell therapy after myocardial infarction acts specifically by enhanced homing via the SDF-1/CXCR4 axisStem Cell Research, 2011
- CXCR7 influences leukocyte entry into the CNS parenchyma by controlling abluminal CXCL12 abundance during autoimmunityThe Journal of Experimental Medicine, 2011
- Matrix Metalloproteinase-9 Mediates Hypoxia-Induced Vascular Leakage in the Brain via Tight Junction RearrangementJournal of Cerebral Blood Flow & Metabolism, 2009
- The inflammatory response in strokeJournal of Neuroimmunology, 2007
- Interleukin 10, monocytes and increased risk of early infection in ischaemic strokeJournal of Neurology, Neurosurgery & Psychiatry, 2006
- Inflammation et accident ischémique cérébral aigu. Données actuelles et perspectivesRevue Neurologique, 2005
- Three or more routes for leukocyte migration into the central nervous systemNature Reviews Immunology, 2003
- Neutrophil inhibitory factor is neuroprotective after focal Ischemia in ratsAnnals of Neurology, 1995
- Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.Stroke, 1986
- Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period.Stroke, 1986