The rol of inmune inhibitory molecule CD200 and its receptor in the developing C57BL/6 mice brain following hypoxia/ischemia

SHRIVASTAVA KALPANA; CHERTOFF, MARIELA; LLOVERA GEMMA; RECASENS MIREIA; ACARIN LAIA; GIMENEZ LLORT LYDIA

BARCELONA

Congreso; FENS FORUM 2012; 2012

FENS

CD200-CD200R system has been widely shown to be involved in inducing immune tolerance and in contributing to immune privileged status of the CNS. However, the developing brain exhibits distinct morphological as well as physiological characteristics determining a peculiar response to injury showing an aggravated susceptibility to excitotoxicity and pro-inflammatory cytokines, along with an exacerbated inflammatory response. Hence, the aim of this study was to characterize the expression pattern of CD200-CD200R in the developing mice brain following Hypoxic/Ischemic (H/I) injury by immunofluorescence. Wild-type C57/BL6 mice postnatal day 7 was used for H/I injury, administered subjecting neonatal mice to 8% O2 for 55 min following unilateral carotid artery occlusion and samples were collected 3h, 12h, 24h, 48h, 72h & 7 days after hypoxia. In control neonatal brains, CD200 was expressed on neurons, blood vessels and some astrocytes, while CD200R was expressed on pial and perivascular macrophages. After H/I, CD200 immunolabeling was increased in the hippocampal fissure until 7 days post-lesion. CD200R+ cells were a subpopulation of Iba1+ reactive microglia/macrophages, showing ameboid/pseudopodic morphologies, and located in the damaged hippocampus and white matter tracts, persisting until 7 days post-lesion. Characterization of CD200R+ cells by triple immunofluorescence showed that most CD200R+ microglia expressed the mannose receptor CD206, characteristic of alternatively activated phenotype M2. In addition, some CD200R+ microglial cells showed markers of antigen presentation such as MHCII and CD86, and in specific survival times also expression of scavenger receptor 1 (CD204). CD200-CD200R molecules are involved in microglial response following neonatal H/I injury.