title: Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice.
abstract: OBJECTIVE
  Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice.
  
  
  METHODS
  C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA.
  
  
  RESULTS
  Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment.
  
  
  CONCLUSIONS
  Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.
authors: Departamento de Bioqufmica e Imunologia, Laboratorio de Imunofarmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. laris.fonseca@gmail.com
authors: Larissa Fonseca da Cunha
authors: LF
authors: Sousa
authors: Fernanda Matos
authors: FM
authors: Coelho
authors: David Henrique
authors: DH
authors: Rodrigues
authors: Alline Cristina
authors: AC
authors: Campos
authors: Luciola da Silva
authors: Lda S
authors: Barcelos
authors: Mauro Martins
authors: MM
authors: Teixeira
authors: Milene Alvarenga
authors: MA
authors: Rachid
authors: Antonio Lucio
authors: AL
authors: Teixeira
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors*; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D020521:Stroke / Q000188:drug therapy*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D013449:Sulfonamides; D009195:Peroxidase; C490707:reparixin
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