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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 orcid ; 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
; ; ; ; ; ; and
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
  • pmid:17937233
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
2024-03-22 13:37:50
@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}},
  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}},
  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}},
  doi          = {{10.3171/JNS-07/10/0844}},
  volume       = {{107}},
  year         = {{2007}},
}