Journal of neurotrauma
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Journal of neurotrauma · Jul 2013
Restoration of neuroendocrine stress response by glucocorticoid receptor or GABA(A) receptor antagonists after experimental traumatic brain injury.
We previously reported that traumatic brain injury (TBI) produced by moderate controlled cortical impact (CCI) attenuates the stress response of the hypothalamic-pituitary-adrenal (HPA) axis between 21 and 70 days postinjury and enhances the sensitivity of the stress response to glucocorticoid negative feedback. In the current study, we investigated two possible mechanisms for the CCI-induced attenuation of the HPA stress response-i.e, glucocorticoid receptor (GR) and GABA-mediated inhibition of the HPA axis, with the GR antagonist, mifepristone (RU486), or the GABA(A)-receptor antagonist, bicuculline. ⋯ Our histological results demonstrate that moderate CCI led to a loss of glutamic acid decarboxylase 67 or parvalbumin-positive inhibitory neurons within regions of the hippocampus and amygdala but did not lead to significant increases in GR in these regions. These findings indicate that suppression of the stress-induced HPA response after moderate CCI is mediated by the inhibitory actions of both GR and GABA, with a corresponding loss of inhibitory neurons within brain regions with neural pathways affecting limbic stress-integrative pathways.
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Journal of neurotrauma · Jul 2013
Profile of self-reported problems with executive functioning in college and professional football players.
Repetitive mild traumatic brain injury (mTBI), such as that experienced by contact-sport athletes, has been associated with the development of chronic traumatic encephalopathy (CTE). Executive dysfunction is believed to be among the earliest symptoms of CTE, with these symptoms presenting in the fourth or fifth decade of life. The present study used a well-validated self-report measure to study executive functioning in football players, compared to healthy adults. ⋯ These symptoms were greater in athletes 40 and older, relative to younger players. In sum, football players reported more-frequent problems with executive functioning and these symptoms may develop or worsen in the fifth decade of life. The findings are in accord with a growing body of evidence that participation in football is associated with the development of cognitive changes and dementia as observed in CTE.
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Journal of neurotrauma · Jul 2013
Treadmill exercise protects against pentylenetetrazol-induced seizures and oxidative stress after traumatic brain injury.
Traumatic brain injury (TBI) is a major cause of acquired epilepsy, and significant resources are required to develop a better understanding of the pathologic mechanism as targets for potential therapies. Thus, we decided to investigate whether physical exercise after fluid percussion injury (FPI) protects from oxidative and neurochemical alterations as well as from behavioral electroencephalographic (EEG) seizures induced by subeffective convulsive doses of pentylenetetrazol (PTZ; 35 mg/kg). Behavioral and EEG recordings revealed that treadmill physical training increased latency to first clonic and tonic-clonic seizures, attenuated the duration of generalized seizures, and protected against the increase of PTZ-induced Racine scale 5 weeks after neuronal injury. ⋯ Exercise training was also effective against alterations in the redox status, herein characterized by lipid peroxidation (thiobarbituric acid reactive substances), protein carbonyl increase, as well as the inhibition of superoxide dismutase and Na⁺,K⁺-ATPase activities after FPI. On the other hand, histologic analysis with hematoxylin and eosin revealed that FPI induced moderate neuronal damage in cerebral cortex 4 weeks after injury and that physical exercise did not protect against neuronal injury. These data suggest that the ability of physical exercise to reduce FPI-induced seizures is not related to its protection against neuronal damage; however, the effective protection of selected targets, such as Na⁺/K⁺-ATPase elicited by physical exercise, may represent a new line of treatment for post-traumatic seizure susceptibility.
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Journal of neurotrauma · Jul 2013
Cortical reorganization after experimental traumatic brain injury: a functional autoradiography study.
Cortical sensorimotor (SM) maps are a useful readout for providing a global view of the underlying status of evoked brain function, as well as a gross overview of ongoing mechanisms of plasticity. Recent evidence in the rat controlled cortical impact (CCI) injury model shows that the ipsilesional (injured) hemisphere is temporarily permissive for axon sprouting. This would predict that size and spatial alterations in cortical maps may occur much earlier than previously tested and that they might be useful as potential markers of the postinjury plasticity period as well as indicators of outcome. ⋯ By 30 days, however, contralesional activation had greatly subsided and existing ipsilesional activity was enhanced within the same novel cortical regions that were identified acutely. These data indicate that significant reorganization of the cortical SM maps occurs after injury that evolves with a particular postinjury time course. We discuss these data in terms of the known mechanisms of plasticity that are likely to underlie these map changes, with particular reference to the differences and similarities that exist between rodent models of stroke and traumatic brain injury.
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Journal of neurotrauma · Jul 2013
ReviewSystems biology approaches for discovering biomarkers for traumatic brain injury.
The rate of traumatic brain injury (TBI) in service members with wartime injuries has risen rapidly in recent years, and complex, variable links have emerged between TBI and long-term neurological disorders. The multifactorial nature of TBI secondary cellular response has confounded attempts to find cellular biomarkers for its diagnosis and prognosis or for guiding therapy for brain injury. ⋯ In addition, we describe opportunities for applying this methodology to existing TBI data sets to identify new biomarker candidates and gain insights about the underlying molecular mechanisms of TBI response. As an exemplar, we apply network and pathway analysis to a manually compiled list of 32 protein biomarker candidates from the literature, recover known TBI-related mechanisms, and generate hypothetical new biomarker candidates.