Journal of neurotrauma
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Journal of neurotrauma · Aug 2009
Temporal and spatial dynamics of peroxynitrite-induced oxidative damage after spinal cord contusion injury.
The reactive nitrogen species peroxynitrite (PN) has been suggested to be an important mediator of the secondary oxidative damage that occurs following acute spinal cord injury (SCI). The PN decomposition products nitrogen dioxide (*NO(2)), hydroxyl radical (*OH), and carbonate radical (*CO(3)) are highly reactive with cellular lipids and proteins. In this immunohistochemical study, we examined the temporal (3, 24, and 72 h, and 1 and 2 weeks) and spatial relationships of PN-mediated oxidative damage in the contusion-injured rat thoracic spinal cord (IH device, 200 kdyn, T10) using 3-nitrotyrosine (3-NT), a marker for protein nitration by PN-derived *NO(2) and 4-hydroxynonenal (4-HNE), an indicator of lipid peroxidation (LP) initiated by any of the PN radicals. ⋯ At all time points except 3 h, there was no significant difference in the mean rostral or caudal extent of 3-NT and 4-HNE staining. By 1, and more so at 2 weeks, the longitudinal extent of the oxidative damage staining was greatly decreased. The spatial and temporal overlap of 3-NT and 4-HNE staining supports the concept that PN is involved in both damage produced by lipid peroxidation and protein nitration, and that antioxidant agents that target PN or PN-derived radicals should be effective neuroprotectants for acute SCI if administered during the first post-injury hours.
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Journal of neurotrauma · Aug 2009
Cauda equina repair in the rat: part 1. Stimulus-evoked EMG for identifying spinal nerves innervating intrinsic tail muscles.
Cauda equina injuries may produce severe leg and pelvic floor dysfunction, for which no effective treatments exist. We are developing a rat cauda equina injury model to allow nerve root identification and surgical repair. One possible difficulty in implementing any repair strategy after trauma in humans involves the correct identification of proximal and distal ends of nerve roots separated by the injury. ⋯ Correctly identifying the level of origin of that root was more difficult, but for ventral roots this rate still exceeded 90%. Using the rat cauda equina model, we have shown that stimulus-evoked EMG can be used to identify ventral nerve roots innervating tail muscles with a high degree of accuracy. These findings support the feasibility of using this conceptual approach for identifying and repairing damaged human cauda equina nerve roots based on stimulus-evoked recruitment of muscles in the leg and pelvic floor.
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Journal of neurotrauma · Aug 2009
Arachidonyl trifluoromethyl ketone is neuroprotective after spinal cord injury.
In spinal cord injury (SCI), neuronal and oligodendroglial loss occurs as a result of the initial trauma and the secondary damage that is triggered by excitotoxicity, free radicals, and inflammation. There is evidence that SCI ellicits increased cytosolic phospholipase A(2) (cPLA(2)) activity. The cleavage of phospholipids by cPLA(2) leads to release of fatty acids, and in particular arachidonic acid (AA), the metabolites of which have been associated with increased inflammation and oxidative stress. ⋯ The number of surviving neurons and oligodendrocytes was significantly increased in animals treated with the cPLA(2) inhibitor compared to saline controls. The behavioral analysis mirrored the neuroprotective effects and showed that the inhibitor-treated group had better locomotor recovery compared to saline controls. Our results show that AACOCF3 has neuroprotective potential, and support the idea that cPLA(2) is critically involved in acute spinal injury.
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Journal of neurotrauma · Aug 2009
Randomized Controlled TrialResuscitation with hypertonic saline-dextran reduces serum biomarker levels and correlates with outcome in severe traumatic brain injury patients.
In the treatment of severe traumatic brain injury (TBI), the choice of fluid and osmotherapy is important. There are practical and theoretical advantages to the use of hypertonic saline. S100B, neuron-specific enolase (NSE), and myelin-basic protein (MBP) are commonly assessed biomarkers of brain injury with potential utility as diagnostic and prognostic indicators of outcome after TBI, but they have not previously been studied in the context of fluid resuscitation. ⋯ HSD-resuscitated patients with favorable outcomes exhibited the lowest serum S100B and NSE concentrations, while maximal levels were found in NS-treated patients with unfavorable outcomes. The lowest biomarker levels were seen in survivors resuscitated with HSD, while maximal levels were in NS-resuscitated patients with fatal outcome. Pre-hospital resuscitation with HSD is associated with a reduction in serum S100B, NSE, and MBP concentrations, which are correlated with better outcome after severe TBI.
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Journal of neurotrauma · Aug 2009
Effect of short periods of normobaric hyperoxia on local brain tissue oxygenation and cerebrospinal fluid oxidative stress markers in severe traumatic brain injury.
Preliminary evidence suggests local brain tissue oxygenation (PbtO(2)) values of