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
Effects of acute intrathecal baclofen in an animal model of TBI-induced spasticity, cognitive, and balance disabilities.
Spasticity is a major health problem for patients with traumatic brain injury (TBI). In addition to spasticity, TBI patients exhibit enduring cognitive, balance, and other motor impairments. Although the use of antispastic medications, particularly ITB, can decrease the severity of TBI-induced spasticity, current guidelines preclude the use of ITB during the first year after TBI. ⋯ Collectively, these data provide a strong molecular footprint of enhanced expression of reflex regulation by presynaptic inhibition. The possibility that acute ITB treatment may decrease maladaptive segmental and descending plasticity is discussed. The data provided by the present animal model initiates a pre-clinical platform for safety, feasibility, and efficacy of early ITB intervention after TBI.
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Journal of neurotrauma · Jul 2013
Rat injury model under controlled field-relevant primary blast conditions: acute response to a wide range of peak overpressures.
We evaluated the acute (up to 24 h) pathophysiological response to primary blast using a rat model and helium driven shock tube. The shock tube generates animal loadings with controlled pure primary blast parameters over a wide range and field-relevant conditions. We studied the biomechanical loading with a set of pressure gauges mounted on the surface of the nose, in the cranial space, and in the thoracic cavity of cadaver rats. ⋯ The immunostaining against immunoglobulin G (IgG) of brain sections of rats sacrificed 24-h post-exposure indicated the diffuse blood-brain barrier breakdown in the brain parenchyma. At high blast intensities (peak overpressure of 190 kPa or more), the IgG uptake by neurons was evident, but there was no evidence of neurodegeneration after 24 h post-exposure, as indicated by cupric silver staining. We observed that the acute response as well as mortality is a non-linear function over the peak overpressure and impulse ranges explored in this work.
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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.
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Journal of neurotrauma · Jul 2013
Triage of children with moderate and severe traumatic brain injury to trauma centers.
Outcomes after pediatric traumatic brain injury (TBI) are related to pre-treatment factors including age, injury severity, and mechanism of injury, and may be positively affected by treatment at trauma centers relative to non-trauma centers. This study estimated the proportion of children with moderate to severe TBI who receive care at trauma centers, and examined factors associated with receipt of care at adult (ATC), pediatric (PTC), and adult/pediatric trauma centers (APTC), compared with care at non-trauma centers (NTC) using a nationally representative database. The Kids' Inpatient Database was used to identify hospitalizations for moderate to severe pediatric TBI. ⋯ Multiple regression analyses showed receipt of care at a trauma center was associated with age and polytrauma. We concluded that almost 84% of children with moderate to severe TBI currently receive care at a Level I or Level II trauma center. Children with trauma to multiple body regions in addition to more severe TBI are more likely to receive care a trauma center relative to a NTC.