Journal of neurotrauma
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Journal of neurotrauma · Sep 2011
Traumatic brain injury in adult rats causes progressive nigrostriatal dopaminergic cell loss and enhanced vulnerability to the pesticide paraquat.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and the accumulation of alpha-synuclein. Both traumatic brain injury (TBI) and pesticides are risk factors for PD, but whether TBI causes nigrostriatal dopaminergic cell loss in experimental models and whether it acts synergistically with pesticides is unknown. We have examined the acute and long-term effects of TBI and exposure to low doses of the pesticide paraquat, separately and in combination, on nigrostriatal dopaminergic neurons in adult male rats. ⋯ At 26 weeks post injury, TBI alone induced a 30% bilateral loss of dopaminergic neurons that was not exacerbated by paraquat. These data suggest that TBI is sufficient to induce a progressive degeneration of nigrostriatal dopaminergic neurons. Furthermore, TBI and pesticide exposure, when occurring within a defined time frame, could combine to increase the PD risk.
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Journal of neurotrauma · Sep 2011
Frequency analysis unveils cardiac autonomic dysfunction after mild traumatic brain injury.
Long-term mortality is increased after mild traumatic brain injury (mTBI). Central cardiovascular-autonomic dysregulation resulting from subtle, trauma-induced brain lesions might contribute to cardiovascular events and fatalities. We investigated whether there is cardiovascular-autonomic dysregulation after mTBI. ⋯ While supine, mTBI patients had reduced cardiovagal modulation and BRS. Upon standing, their BRS was still reduced, and patients did not withdraw parasympathetic or augment sympathetic modulation adequately. Impaired autonomic modulation probably contributes to cardiovascular irregularities post-mTBI.
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Journal of neurotrauma · Sep 2011
A voxel-based analysis of FDG-PET in traumatic brain injury: regional metabolism and relationship between the thalamus and cortical areas.
The objective was to study the correlations and the differences in glucose metabolism between the thalamus and cortical structures in a sample of severe traumatic brain injury (TBI) patients with different neurological outcomes. We studied 49 patients who had suffered a severe TBI and 10 healthy control subjects using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). The patients were divided into three groups: a vegetative or minimally-conscious state (MCS&VS) group (n=17), which included patients who were in a vegetative or a minimally conscious state; an In-post-traumatic amnesia (In-PTA) group (n=12), which included patients in PTA; and an Out-PTA group (n=20), which included patients who had recovered from PTA. ⋯ Voxel-based analysis suggests a functional correlation between these four areas, and decreased metabolism was associated with less favorable outcomes. Higher levels of activation of the cortico-cortical connections appear to be related to better neurological condition. Differences in the thalamo-cortical correlations between patients and controls may be related to traumatic dysfunction due to focal or diffuse lesions.
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Journal of neurotrauma · Sep 2011
Detrimental effect of genetic inhibition of B-site APP-cleaving enzyme 1 on functional outcome after controlled cortical impact in young adult mice.
β-Amyloid (Aβ) peptides, most notably associated with Alzheimer's disease, have been implicated in the pathogenesis of secondary injury after traumatic brain injury (TBI). A prior study has demonstrated that blocking the β-site amyloid precursor protein (APP)-cleaving enzyme 1 (Bace1) required for production of Aβ from APP improved functional and histologic outcomes after controlled cortical impact (CCI) in aged mice. However, the majority of patients with severe TBI are young adults under the age of 40. ⋯ Soluble Aβ(40) was significantly lower in ipsilateral hemispheres of Bace1(-/-) than in Bace1(+/+) animals after CCI (0.9 [IQR 0.88-0.94] pmol/g protein versus 3.8 [IQR 2.4-6.0] pmol/g protein; p=0.005). Lesion and hippocampal volumes did not differ between injured groups. The data suggest that therapies targeting Bace1 may need to be tailored according to age and injury severity, as their use may exacerbate functional deficits after TBI in younger or less severely injured patients.
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Journal of neurotrauma · Sep 2011
Cerebrovascular connexin expression: effects of traumatic brain injury.
Traumatic brain injury (TBI) results in dysfunction of the cerebrovasculature. Gap junctions coordinate vasomotor responses and evidence suggests that they are involved in cerebrovascular dysfunction after TBI. Gap junctions are comprised of connexin proteins (Cxs), of which Cx37, Cx40, Cx43, and Cx45 are expressed in vascular tissue. ⋯ Western blot analysis revealed that Cx40 protein expression increased, while Cx45 protein expression decreased 24 h after injury. These studies revealed significant changes in the mRNA and protein expression of specific vascular Cxs after TBI. This is the first demonstration of cell type-related differential expression of Cx mRNA in cerebral arteries, and is a first step in evaluating the effects of TBI on gap junction communication in the cerebrovasculature.