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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

Marklund, Niklas LU ; Bareyre, Florence M; Royo, Nicolas C; Thompson, Hilaire J; Mir, Anis K; Grady, M Sean; Schwab, Martin E and McIntosh, Tracy K (2007) In Journal of Neurosurgery 107(4). p.53-844
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
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
in
Journal of Neurosurgery
volume
107
issue
4
pages
10 pages
publisher
American Association of Neurosurgeons
external identifiers
  • scopus:35148891642
ISSN
0022-3085
DOI
10.3171/JNS-07/10/0844
language
English
LU publication?
no
id
1e34719a-b767-453e-85b6-d3b22fca24db
date added to LUP
2016-12-08 12:18:57
date last changed
2017-11-05 05:10:49
@article{1e34719a-b767-453e-85b6-d3b22fca24db,
  abstract     = {<p>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.</p><p>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.</p><p>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 &lt; 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 &lt; 0.05).</p><p>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.</p>},
  author       = {Marklund, Niklas and Bareyre, Florence M and Royo, Nicolas C and Thompson, Hilaire J and Mir, Anis K and Grady, M Sean and Schwab, Martin E and McIntosh, Tracy K},
  issn         = {0022-3085},
  keyword      = {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},
  language     = {eng},
  number       = {4},
  pages        = {53--844},
  publisher    = {American Association of Neurosurgeons},
  series       = {Journal of Neurosurgery},
  title        = {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},
  url          = {http://dx.doi.org/10.3171/JNS-07/10/0844},
  volume       = {107},
  year         = {2007},
}