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Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

Marq-Lin, N.
Rodriguez, I.
Published in British Journal of Pharmacology. 2010, vol. 160, no. 2, p. 311-321
Abstract BACKGROUND AND PURPOSE: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. EXPERIMENTAL APPROACH: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. KEY RESULTS: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. CONCLUSIONS AND IMPLICATIONS: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1-2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs.
Keywords AnimalsAstrocytes/metabolismBrain Ischemia/ physiopathologyDisease Models, AnimalInfarction, Middle Cerebral Artery/pathologyMaleMiceMice, Inbred C57BLMice, KnockoutMicroglia/metabolismMotor ActivityNeutrophils/ metabolismReceptors, CCR5/ geneticsSeverity of Illness IndexTime Factors
Stable URL http://archive-ouverte.unige.ch/unige:11590
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PMID: 20423342
Research groups Radicaux libres et cellules souches embryonnaires (60)
Groupe Schaller Karl-Lothard (neurochirurgie) (851)
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