title: Inhibition of Nogo-66 receptor 1 enhances recovery of cognitive function after traumatic brain injury in mice.
abstract: Central nervous system (CNS) axons recover poorly following injury because of the expression of myelin-derived inhibitors of axonal outgrowth such as Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp), all of which bind to the Nogo-66 receptor 1 (NgR1). Herein we examine the role of NgR1 in the recovery of motor and cognitive function after traumatic brain injury (TBI) using a controlled cortical impact (CCI) model in NgR1 knockout (KO) and wild-type (WT) mice. Four weeks post-injury, scores on the Novel Object Recognition test were significantly increased in NgR1 KO mice compared with WT mice (p<0.05), but motor behavior test scores did not differ significantly between the two groups. Nissl staining showed that NgR1 KO mice had less brain injury volume 2 weeks after CCI (p<0.05). Histological analysis revealed more doublecortin (DCX+) cells (p<0.01) and more Ki-67+ cells in the contralateral dentate gyrus (DG) (p<0.05) 2 weeks after CCI in NgR1 KO mice than in WT. Furthermore, DCX+ cells still retained their longer processes in KO mice (p<0.01) 4 weeks following trauma. The number of bromodeoxyuridine (BrdU)+ cells did not differ between the two groups at 4 weeks post-trauma, but KO mice had higher numbers of cells that co-stained with NeuN, a marker of mature neurons. Increased transcription of growth-associated protein (GAP)-43 in both the injured and contralateral sides of the hippocampus (both p<0.05) was detected in NgR1 KO mice relative to WT. These data suggest that NgR1 negatively influences plasticity and cognitive recovery after TBI.
authors.affiliation: Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Tong
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Han
authors.forename: Ollivier
authors.initials: O
authors.lastname: Hyrien
authors.forename: Uzma
authors.initials: U
authors.lastname: Samadani
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
authors.forename: Jason H
authors.initials: JH
authors.lastname: Huang
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D058851:GPI-Linked Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009185:Myelin Proteins / Q000378:metabolism*; D000070816:Nogo Receptor 1; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse