Cognitive outcome following brain injury and treatment with an inhibitor of Nogo-A in association with an attenuated downregulation of hippocampal growth-associated protein-43 expression
2007 (English)In: Journal of Neurosurgery, ISSN 0022-3085, Vol. 107, no 4, 844-853 p.Article in journal (Refereed) Published
Object. Central nervous system axons regenerate poorly after traumatic brain injury (TBI), partly due to inhibitors such as the protein Nogo-A present in myelin. The authors evaluated the efficacy of anti-Nogo-A monoclonal antibody (mAb) 7B 12 administration on the neurobehavioral and cognitive outcome of rats following lateral fluid-percussion brain injury, characterized the penetration of the 7B 12 or control antibodies into target brain regions, and evaluated the effects of Nogo-A inhibition on hemispheric tissue loss and sprouting of uninjured motor tracts in the cervical cord. To elucidate a potential molecular response to Nogo-A inhibition, we evaluated the effects of 7B 12 on hippocampal GAP-43 expression. Methods. Beginning 24 hours after lateral fluid-percussion brain injury or sham injury in rats, the mAb 7B12 or control antibody was infused intracerebroventricularly over 14 days, and behavior was assessed over 4 weeks. Results. Immunoreactivity for 7B 12 or immunoglobulin G was detected in widespread brain regions at 1 and 3 weeks postinjury. The brain-injured animals treated with 7B12 showed improvement in cognitive function (p < 0.05) at 4 weeks but no improvement in neurological motor function from 1 to 4 weeks postinjury compared with brain-injured, vehicle-treated controls. The enhanced cognitive function following inhibition of Nogo-A was correlated with an attenuated postinjury downregulation of hippocampal GAP-43 expression (p < 0.05). Conclusions. Increased GAP-43 expression may be a novel molecular mechanism of the enhanced cognitive recovery mediated by Nogo-A inhibition after TBI in rats.
Place, publisher, year, edition, pages
2007. Vol. 107, no 4, 844-853 p.
Nervous system diseases, Regeneration, Cognition, Growth associated protein 43, Hippocampus, Treatment, Encephalon, Prognosis, Head trauma
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-15359DOI: 10.3171/JNS-07/10/0844ISI: 000249746500021PubMedID: 17937233OAI: oai:DiVA.org:uu-15359DiVA: diva2:43130