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
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
Combining whole-brain voxel-wise analysis with in vivo tractography of diffusion behavior after sports-related concussion in adolescents: a preliminary report.
We have previously shown that sports-related concussion in adolescents is associated with changes in whole-brain properties of white-matter pathways. Here, we assess local changes within these pathways. Twelve adolescents with a clinical diagnosis of subacute concussion and 10 healthy adolescents matched for age, gender, and physical activity completed magnetic resonance imaging scanning. ⋯ Fractional anisotropy within the reconstructed tracts was not significantly different between the two groups. These results suggest that subacute concussion in adolescents is associated with altered diffusion properties within regional white-matter tissue and along reconstructed fiber pathways. Combining voxel-wise analysis with fiber tractography provides an alternative objective approach to evaluate and identify subtle changes in white-matter fiber integrity after concussion.
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The present study tested a hypothesis that early identification of injury severity with quantitative magnetic resonance imaging (MRI) provides biomarkers for predicting increased seizure susceptibility and epileptogenesis after traumatic brain injury (TBI). TBI was induced by lateral fluid percussion injury (FPI) in adult rats. Quantitative T2, T1ρ, and diffusion were assessed with MRI at 9 days, 23 days, or 2 months post-TBI in the perilesional cortex, thalamus, and hippocampus. ⋯ At 2 months post-TBI, Dav in the thalamus was the best of the biomarkers analyzed (AUC, 0.988; p<0.05). The highest predictive value of all biomarkers was achieved by combining the measurement of Dav in the perilesional cortex and the thalamus at 2 months post-TBI (AUC, 1.000; p<0.01). Our results provide proof-of-concept evidence that clinically relevant MRI biomarkers predict increased seizure susceptibility after experimental TBI.
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Journal of neurotrauma · Jul 2013
Transcranial magnetic stimulation-electroencephalography responses in recovered and symptomatic mild traumatic brain injury.
Mild traumatic brain injury (mTBI) may cause diffuse damage to the brain, especially to the frontal areas, that may lead to persistent symptoms. We studied participants with past mTBI by means of navigated transcranial magnetic stimulation (nTMS) combined with electroencephalography (EEG). Eleven symptomatic and 8 recovered participants with a history of single mTBI and 9 healthy controls participated. ⋯ In left M1 nTMS, the mTBI groups showed less P30 amplitude increase, and the symptomatic group showed longer P60 interhemispheric latency difference with higher stimulation intensities. The results suggest altered brain reactivity and connectivity in mTBI. Some of the observed differences may be related to compensatory mechanisms of recovery. nTMS-EEG is a potentially useful tool for studying the effects of mTBI.