title: Brain recovery mediated by toll-like receptor 4 in rats after intracerebral hemorrhage.
abstract: Activation of the immune system via toll-like receptor 4 (TLR4) is implicated in both negative and positive processes in the central nervous system, including inflammation and angiogenesis. Whether TLR4 also participates in brain recovery following intracerebral hemorrhage (ICH) has not been investigated. We used the rat model of collagenase-induced ICH to determine whether TLR4 acts as a key regulator of brain recovery in the late phase of injury. After ICH, TLR4 levels in the ipsilateral striatum were significantly higher in the ICH group than in the Sham group on days 1, 3, 7 and 14 after ICH induction. By 14 d, the ICH group showed significantly higher levels of vascular endothelial growth factor, brain-derived neurotrophic factor, and MMP-9 than the Sham group, as well as greater numbers of vessels and BrdU- and DCX-positive cells. All these ICH-induced increases were significantly smaller in the TAK-242 group. The TLR4 antagonist also inhibited the recovery of neurological function after ICH. A TLR4 antagonist reduced ICH-induced neurogenesis and angiogenesis in a rat. These findings suggest that TLR4 may promote brain repair in the late phase of ICH.
authors.affiliation: Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Lei
authors.affiliation: Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, PR China; State Key Laboratory of Human Disease Biotherapy and Ministry of Education, West China Hospital, Sichuan University, PR China. Electronic address: dragonwbtxf@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, PR China.
authors.forename: Tian
authors.initials: T
authors.lastname: Cao
authors.affiliation: Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, PR China; State Key Laboratory of Human Disease Biotherapy and Ministry of Education, West China Hospital, Sichuan University, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, PR China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Hao
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000633:toxicity; D000089662:Doublecortin Protein; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D013449:Sulfonamides; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; D003094:Collagen
keywords: Angiogenesis; Intracerebral hemorrhage; Neurogenesis; Toll-like receptor-4