Inhibition of Nogo-66 receptor 1 enhances recovery of cognitive function after traumatic brain injury in mice.
J Neurotrauma
; 30(4): 247-58, 2013 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-22967270
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Injuries
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Cognition
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Receptors, Cell Surface
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Recovery of Function
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Motor Activity
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Myelin Proteins
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Neurotrauma
Journal subject:
NEUROLOGIA
/
TRAUMATOLOGIA
Year:
2013
Document type:
Article
Affiliation country: