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Functional outcome is impaired following traumatic brain injury in aging Nogo-A/B-deficient mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
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2009 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 163, no 2, 540-551 p.Article in journal (Refereed) Published
Abstract [en]

Increasing age is associated with a poor prognosis following traumatic brain injury (TBI). CNS axons may recover poorly following TBI due to expression of myelin-derived inhibitors to axonal outgrowth such as Nogo-A. To study the role of Nogo-A/B in the pathophysiological response of the elderly to TBI, 1-year-old mice deficient in Nogo-A/B (Nogo-A/B homozygous(-/-) mice), Nogo-A/B heterozygous(-/+) mice, and age-matched wild-type (WT) littermate controls were subjected to a controlled cortical impact (CCI) TBI. Sham-injured WT mice (7 months old) and 12 month old naïve Nogo-A/B(-/-) and Nogo-A/B(-/+) served as controls. Neurological motor function was evaluated up to 3 weeks, and cognitive function, hemispheric tissue loss, myelin staining and hippocampal beta-amyloid (A beta) immunohistochemistry were evaluated at 4 weeks post-injury. In WT littermates, TBI significantly impaired learning ability at 4 weeks and neurological motor function up to 2 weeks post-injury and caused a significant loss of hemispheric tissue. Following TBI, Nogo-A/B(-/-) mice showed significantly less recovery from neurological motor and cognitive deficits compared to brain-injured WT mice. Naïve Nogo-A/B(-/-) and Nogo-A/B(-/+) mice quickly learned the MWM task in contrast to brain-injured Nogo-A/B(-/-) mice who failed to learn the MWM task at 4 weeks post-injury. Hemispheric tissue loss and cortical lesion volume were similar among the brain-injured genotypes. Neither TBI nor the absence of NogoA/B caused an increased A beta expression. Myelin staining showed a reduced area and density in the corpus callosum in brain-injured Nogo-A/B(-/-) animals compared to their littermate controls. These novel and unexpected behavioral results demonstrate that the absence of Nogo-A/B may negatively influence outcome, possibly related to hypomyelination, following TBI in mice and suggest a complex role for this myelin-associated axonal growth inhibitor following TBI.

Place, publisher, year, edition, pages
2009. Vol. 163, no 2, 540-551 p.
Keyword [en]
traumatic brain injury, Nogo-A, Nogo-B, Morris water maze, neurological motor deficits
National Category
Physiology
Research subject
Neurosurgery
Identifiers
URN: urn:nbn:se:uu:diva-120404DOI: 10.1016/j.neuroscience.2009.06.042ISI: 000269967800005PubMedID: 19555742OAI: oai:DiVA.org:uu-120404DiVA: diva2:303285
Available from: 2010-03-11 Created: 2010-03-11 Last updated: 2011-11-17Bibliographically approved

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Clausen, FredrikHånell, Anders

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