Journal of neurotrauma
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Abstract Chronic subdural hematoma is a frequent disorder in the elderly. Although intensively investigated, numerous aspects, including the pathophysiology of clinical symptoms, remain unclear. Perfusion deficits are likely to induce the transient neurologic symptoms seen in chronic subdural hematoma (cSDH). ⋯ CBV and CBF are significantly upregulated in the cortical area below cSDH indicating the effect of autoregulation in tissue at risk of ischemia. Cerebral autoregulation is intact in cSDH. Neurologic deficits are likely induced by borderline perfusion.
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Journal of neurotrauma · Mar 2013
Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury.
Abstract Traumatic brain injury (TBI) induces microglial activation, which can contribute to secondary tissue loss. Activation of mGluR5 reduces microglial activation and inhibits microglial-mediated neurodegeneration in vitro, and is neuroprotective in experimental models of CNS injury. In vitro studies also suggest that the beneficial effects of mGluR5 activation involve nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition in activated microglia. ⋯ To address whether the neuroprotective effects of CHPG are mediated via the inhibition of NADPH oxidase, we administered the NADPH oxidase inhibitor apocynin with or without CHPG treatment after TBI. Both apocynin or CHPG treatment alone improved sensorimotor deficits and reduced lesion volumes when compared with vehicle-treated mice; however, the combined CHPG + apocynin treatment was not superior to CHPG alone. These data suggest that the neuroprotective effects of activating mGluR5 receptors after TBI are mediated, in part, via the inhibition of NADPH oxidase.
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Journal of neurotrauma · Mar 2013
Concussive injury before or after controlled cortical impact exacerbates histopathology and functional outcome in a mixed traumatic brain injury model in mice.
Traumatic brain injury (TBI) may involve diverse injury mechanisms (e.g., focal impact vs. diffuse impact loading). Putative therapies developed in TBI models featuring a single injury mechanism may fail in clinical trials if the model does not fully replicate multiple injury subtypes, which may occur concomitantly in a given patient. We report development and characterization of a mixed contusion/concussion TBI model in mice using controlled cortical impact (CCI; 0.6 mm depth, 6 m/sec) and a closed head injury (CHI) model at one of two levels of injury (53 vs. 83 g weight drop from 66 in). ⋯ Additive effects of CHI and CCI on post-injury motor (p<0.05) and cognitive (p<0.005) impairment were observed with sequential CCI-CHI (83 g). The data suggest that concussive forces, which in isolation do not induce histopathological damage, exacerbate histopathology and functional outcome after cerebral contusion. Sequential CHI-CCI may model complex injury mechanisms that occur in some patients with TBI and may prove useful for testing putative therapies.
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Journal of neurotrauma · Mar 2013
Roles of chondroitin sulfate and dermatan sulfate in the formation of a lesion scar and axonal regeneration after traumatic injury of the mouse brain.
Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. ⋯ The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration.
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Journal of neurotrauma · Feb 2013
Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, and endothelial damage in patients with traumatic brain injury.
It remains to be debated whether traumatic brain injury (TBI) induces a different coagulopathy than does non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy, and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients was sampled (median of 68 min [IQR 48-88] post-injury) upon admission to our trauma center. ⋯ No significant biomarker differences were found between isoTBI and non-TBI patients. Injury severity scale (ISS) rather than the presence or absence of head/neck injuries determined the hemostatic and biomarker response to the injury. The coagulopathy identified thus reflected the severity of injury rather than its localization.