Functional outcome is impaired following traumatic brain injury in aging Nogo-A/B-deficient mice
2009 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 163, no 2, 540-551 p.Article in journal (Refereed) Published
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.
traumatic brain injury, Nogo-A, Nogo-B, Morris water maze, neurological motor deficits
Research subject Neurosurgery
IdentifiersURN: urn:nbn:se:uu:diva-120404DOI: 10.1016/j.neuroscience.2009.06.042ISI: 000269967800005PubMedID: 19555742OAI: oai:DiVA.org:uu-120404DiVA: diva2:303285