title: Toll-like receptor 4 is involved in ischemic tolerance of postconditioning in hippocampus of tree shrews to thrombotic cerebral ischemia.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) is an important mediator of the innate immune response. It significantly contributes to neuroinflammation and may be involved in ischemic tolerance. It is unknown how cerebral ischemia in the cortex and postconditioning might affect inflammatory reactions in the hippocampus or whether TLR4 expression plays a role.
  
  
  OBJECTIVE
  This study explored the mechanistic hypothesis that postconditioning modulates TLR4 expression and thus improves inflammatory reactions in the hippocampus.
  
  
  METHODS
  Thrombotic focal cerebral ischemia was induced by a photochemical reaction in tree shrews. Four hours after the photochemical reaction onset, ischemic postconditioning was established with three repeated five minute cycles of temporary right carotid artery clipping and a five minute reperfusion. Histological changes were assessed over 72h in hippocampal morphology (hematoxylin-and-eosin), myeloperoxidase (MPO) expression (immunohistochemistry), TLR4 expression (Western blot analysis and immunohistochemistry), and TLR4 mRNA expression (semiquantitative RT-PCR).
  
  
  RESULTS
  We found extensive neuronal degeneration in the hippocampus that peaked at 24h after cerebral ischemia. This was significantly attenuated after postconditioning. Cerebral ischemia caused a predominant increase in TLR4 protein expression from 4 to 24h (P<0.05). In contrast, postconditioning caused a decrease in TLR4 protein expression from 4 to 24h (P<0.05), which increased at 72h (P<0.05). Hippocampal TLR4 mRNA levels showed the same trends as those observed in protein expression.
  
  
  CONCLUSIONS
  These findings indicated that TLR4 signaling and innate immunity may be involved in the protective mechanisms of postconditioning and ischemic tolerance.
authors.affiliation: Department of Rheumatology and Immunology, The first Affiliated Hospital of Kunming Medical University, Kunming 650031, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Shuqing
authors.initials: S
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014418:Tupaiidae
chemical_list: D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D009195:Peroxidase