Journal of neurotrauma
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Journal of neurotrauma · Sep 2011
The association between apolipoprotein E and traumatic brain injury severity and functional outcome in a rehabilitation sample.
Traumatic brain injury (TBI) can result in significant disability, but outcome is variable. The impact of known predictors accounts for a limited proportion of the variance in outcomes. Apolipoprotein E (ApoE) genotype has been investigated as an additional source of variability in injury severity and outcome, with mixed findings reflecting variable methodology and generally limited sample sizes. ⋯ Prediction of worse Glasgow Outcome Scale-Extended (GOSE) scores for ɛ4 carriers was supported with greater susceptibility seen in females. These results indicate the ApoE ɛ4 allele may be associated with poorer long-term outcome, but not acute injury severity. Possible mechanisms include differential effects of the ɛ4 allele on inflammatory and cellular repair processes, and/or amyloid deposition.
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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
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
Post-injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats.
Mitochondrial dysfunction is known to play a pivotal role in cell death mechanisms following traumatic brain injury (TBI). N-methyl-4-isoleucine-cyclosporin (NIM811), a non-immunosuppressive cyclosporin A (CsA) analog, inhibits the mitochondrial permeability transition pore (mPTP) and has been shown to be neuroprotective following TBI in mice. However, the translation of the neuroprotective effects of mPTP inhibitors, including CsA and NIM811, into improved cognitive end points has yet to be fully investigated. ⋯ For behavioral studies, rats were administered NIM811 at 15 min and 24 h post-injury, with cognitive testing beginning 10 days post-injury. Mitochondrial studies involved a single injection of NIM811 at 15 min post-injury followed by mitochondrial isolation at 6 h post-injury. The results revealed that the optimal dose of NIM811 improves cognition, improves mitochondrial functioning, and reduces oxidative damage following TBI.
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Journal of neurotrauma · Sep 2011
Anti-inflammatory treatments during the chronic phase of spinal cord injury improve locomotor function in adult mice.
Our previous data suggested that ongoing inflammation in the spinal cord 6 weeks following spinal cord injury was detrimental to locomotor function. Others have shown in the acute and sub-acute post-injury phase that microglial/macrophage activation and T regulatory cells are detrimental to recovery. Here, C57BL/6 mice with a moderately severe T9 contusion were injected intravenously daily with minocycline, which reduces microglial/macrophage activation, or with CD25 antibodies, which reduce T regulatory cell function, starting at 6 weeks after injury. ⋯ The effects diminished within 1 week after termination of the treatments, suggesting an ongoing and dynamic inflammatory process. The area of white matter or the inflammatory markers CD68 for activated microglia/macrophages and CD45 for leukocytes were not different between the groups. These data suggest that inflammation during the chronic phase following spinal cord injury reduces conduction through the epicenter, possibly by release of cytokines, and is amenable to treatment for improved neurological function.