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

Niklas Marklund, Florence M Bareyre, Nicolas C Royo, Hilaire J Thompson, Anis K Mir, M Sean Grady, Martin E Schwab, Tracy K McIntosh

Research output: Contribution to journalArticlepeer-review

35 Citations (SciVal)

Abstract

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) 7B12 administration on the neurobehavioral and cognitive outcome of rats following lateral fluid-percussion brain injury, characterized the penetration of the 7B12 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 7B12 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 7B12 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.

Original languageEnglish
Pages (from-to)844-53
Number of pages10
JournalJournal of Neurosurgery
Volume107
Issue number4
DOIs
Publication statusPublished - 2007 Oct
Externally publishedYes

Keywords

  • Animals
  • Antibodies, Monoclonal
  • Behavior, Animal
  • Brain Injuries
  • Cerebral Cortex
  • Cognition
  • Down-Regulation
  • GAP-43 Protein
  • Hippocampus
  • Immunoglobulin G
  • Male
  • Myelin Proteins
  • Nerve Fibers, Myelinated
  • Nerve Regeneration
  • Rats
  • Rats, Sprague-Dawley
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this