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Behavioral and histopathological alterations resulting from mild fluid percussion injury.

ABSTRACT: The majority of people who sustain a traumatic brain injury (TBI) have an injury that can be classified as mild (often referred to as concussion). Although head CT scans for most subjects who have sustained a mild TBI (mTBI) are negative, these persons may still suffer from neurocognitive and neurobehavioral deficits. In order to expedite pre-clinical research and develop therapies, there is a need for well-characterized animal models of mTBI that reflect the neurological, neurocognitive, and pathological changes seen in human patients. In the present study, we examined the motor, cognitive, and histopathological changes resulting from 1.0 and 1.5 atmosphere (atm) overpressure fluid percussion injury (FPI). Both 1.0 and 1.5 atm FPI injury caused transient suppression of acute neurological functions, but did not result in visible brain contusion. Animals injured with 1.0 atm FPI did not show significant motor, vestibulomotor, or learning and memory deficits. In contrast, 1.5 atm injury caused transient motor disturbances, and resulted in a significant impairment of spatial learning and short-term memory. In addition, 1.5 atm FPI caused a marked reduction in cerebral perfusion at the site of injury that lasted for several hours. Consistent with previous studies, 1.5 atm FPI did not cause visible neuronal loss in the hippocampus or in the neocortex. However, a robust inflammatory response (as indicated by enhanced GFAP and Iba1 immunoreactivity) in the corpus callosum and the thalamus was observed. Examination of fractional anisotropy color maps after diffusion tensor imaging (DTI) revealed a significant decrease of FA values in the cingulum, an area found to have increased silver impregnation, suggesting axonal injury. Increased silver impregnation was also observed in the corpus callosum, and internal and external capsules. These findings are consistent with the deficits and pathologies associated with mild TBI in humans, and support the use of mild FPI as a model to evaluate putative therapeutic options.

SUBMITTER: Hylin MJ

PROVIDER: S-EPMC3941923 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:After the initial insult in traumatic brain injury (TBI), secondary neurodegeneration occurs that is intimately associated with neuroinflammation. Prostaglandin (PG) synthases and cyclooxygenase (COX) 1 and 2 may contribute to inflammation in the brain. Temporal and spatial expression features of PG and COX1 and 2 following trauma may guide the development of antineuroinflammation strategies. Here, we examined PG synthase signaling and COX1 and 2 gene expression levels and COX-1- and 2-positive cell types and their temporal localization in TBI-induced brain in an effort to reveal their participation in the disease's evolving neuroinflammation. Using brain samples from the cerebral cortex of rats subjected to TBI model of lateral moderate fluid percussion injury (FPI), we sought to characterize the temporal (subacute TBI) and spatial (lateral cortical lesion) brain alterations accompanying the disease progression. Temporal gene expression changes of PG synthase signaling were compared between sham-operated and TBI-treated rats using microarray pathway analysis. Moreover, we examined COX1 and 2 expression patterns and their intracellular distribution in sham-operated and TBI-treated rats by immunohistochemistry. After FPI, COX1 and 2 gene expression levels, and PGE2 synthase increased while PGD2 synthase decreased, suggesting that PGE2 and PGD2 afforded contraindicative effects of inflammation and anti-inflammation, respectively. Immunohistochemical analyses showed that both COX1 and COX2 increased in a time-dependent manner in the brain, specifically in degenerating neurons of the cortex. Interestingly, the expression of COX cell type was cell-specific, in that COX1 was particularly increased in degenerating neurons while COX2 was expressed in macrophages. In view of the dynamic temporal and spatial expression of PG, COX1 and 2 gene expression and localization in the injured brain regulating PG synthase and COX1 and 2 activity will require a careful disease-specific tailoring of treatments to abrogate the neuroinflammation-plagued secondary cell death due to TBI.

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Behavioral and histopathological alterations resulting from mild fluid percussion injury.

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