Differential regulation of the CXCR2 chemokine network in rat brain trauma: Implications for neuroimmune interactions and neuronal survival

Autor: Astrid Vallès, Lindsay Grijpink-Ongering, Freddy M. de Bree, Tinka Tuinstra, Eric Ronken
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: Neurobiology of Disease, Vol 22, Iss 2, Pp 312-322 (2006)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2005.11.015
Popis: Chemokine receptors represent promising targets to attenuate inflammatory responses and subsequent secondary damage after brain injury. We studied the response of the chemokines CXCL1/CINC-1 and CXCL2/MIP-2 and their receptors CXCR1 and CXCR2 after controlled cortical impact injury in adult rats. Rapid upregulation of CXCL1/CINC-1 and CXCL2/MIP-2, followed by CXCR2 (but not CXCR1), was observed after injury. Constitutive neuronal CXCR2 immunoreactivity was detected in several brain areas, which rapidly but transiently downregulated upon trauma. A second CXCR2-positive compartment, mainly colocalized with the activated microglia/macrophage marker ED1, was detected rapidly after injury in the ipsilateral cortex, progressively emerging into deeper areas of the brain later in time. It is proposed that CXCR2 has a dual role after brain injury: (i) homologous neuronal CXCR2 downregulation would render neurons more vulnerable to injury, whereas (ii) chemotaxis and subsequent differentiation of blood-borne cells into a microglial-like phenotype would be promoted by the same receptor.
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