Regulation of Toll-like receptor 1 and -2 in neonatal mice brains after hypoxia-ischemia

Background: hypoxic-ischemic (hi) brain injury remains a major problem in newborns,resulting in increased risk of neurological disorders. neonatal hi triggers a broad inflammatory reaction in the brain,including activation of the innate immune system. toll-like receptors (tlrs),which are key components of the innate immune system,are believed to play a role in adult cerebral ischemic injury. the expression of tlrs in the neonatal brain and their regulation after hi is unknown.methods: wild type c57bl/6,tlr 1 knockout (ko) and tlr 2 ko mice were subjected to hi at postnatal day 9 and sacrificed 30 min,6 h,24 h or 5 days after hi. tlr mrna expression was determined by rt-qpcr and protein and cell type localisation by immunohistochemistry (ihc). to evaluate brain injury,infarct volume was measured in the injured hemisphere.results: mrna expression was detected for all investigated tlrs (tlr1-9),both in normal and hi exposed brains. after hi,tlr-1 was down-regulated at 30 min and up-regulated at 6 h and 24 h. tlr-2 was up-regulated at 6 h and 24 h,and tlr-7 at 24 h. both tlr-5 and tlr-8 were down-regulated at 24 h and 30 min respectively. ihc showed an increase of tlr-1 in neurons in the ipsilateral hemisphere after hi. tlr-2 was constitutively expressed in astrocytes and in a population of neurons in the paraventricular nucleus in the hypothalamus. no changes in expression were detected following hi. following hi,tlr-2 ko mice,but not tlr-1 ko,showed a decreased infarct volume compared to wild type (p = 0.0051).conclusions: this study demonstrates that tlrs are regulated after hi in the neonatal brain. tlr-1 protein was up-regulated in injured areas of the brain but tlr-1 ko animals were not protected from hi. in contrast,tlr-2 was constitutively expressed in the brain and tlr-2 deficiency reduced hi injury. these data suggest that tlr-2,but not tlr-1,plays a role in neonatal hi brain injury. © 2011 stridh et al; licensee biomed central ltd.