title: Absence of TLR4 reduces neurovascular unit and secondary inflammatory process after traumatic brain injury in mice.
abstract: BACKGROUND
  Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. Toll-like receptors (TLRs) are signaling receptors in the innate immune system, although emerging evidence indicates their role in brain injury. We have therefore investigated the role played by TLR4 signaling pathway in the development of mechanisms of secondary inflammatory process in traumatic brain injury (TBI) differ in mice that lack a functional TLR4 signaling pathway.
  
  
  RESULTS
  Controlled cortical impact injury was performed on TLR4 knockout (KO) mice (C57BL/10ScNJ) and wild-type (WT) mice (C57BL/10ScNJ). TBI outcome was evaluated by determination of infarct volume and assessment of neurological scores. Brains were collected at 24 h after TBI. When compared to WT mice, TLR4 KO mice had lower infarct volumes and better outcomes in neurological and behavioral tests (evaluated by EBST and rotarod test). Mice that lacked TLR4 had minor expression of TBI-induced GFAP, Chymase, Tryptase, IL-1β, iNOS, PARP and Nitrotyrosine mediators implicated in brain damage. The translocation of expression of p-JNK, IκB-α and NF-κB pathway were also lower in brains from TLR4 KO mice. When compared to WT mice, resulted in significant augmentation of all the above described parameters. In addition, apoptosis levels in TLR4 KO mice had minor expression of Bax while on the contrary with Bcl-2.
  
  
  CONCLUSIONS
  Our results clearly demonstrated that absence of TLR4 reduces the development of neuroinflammation, tissues injury events associated with brain trauma and may play a neuroprotective role in TBI in mice.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, Messina, Italy.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.forename: Michela
authors.initials: M
authors.lastname: Campolo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D005904:Glial Fibrillary Acidic Protein; D020672:I-kappa B Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D053802:Tryptases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C000606205:Nfkbia protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C528900:glial fibrillary astrocytic protein, mouse; D000072000:NF-KappaB Inhibitor alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D048670:MAP Kinase Kinase 4; D053802:Tryptases
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