Journal of neurotrauma
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Journal of neurotrauma · Aug 2002
NBQX treatment improves mitochondrial function and reduces oxidative events after spinal cord injury.
The purpose of this study was to examine the effects of inhibiting ionotropic glutamate receptor subtypes on measures of oxidative stress events at acute times following traumatic spinal cord injury (SCI). Rats received a moderate contusion injury and 15 min later were treated with one of two doses of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulfonamide disodium (NBQX), MK-801, or the appropriate vehicle. At 4 h following injury, spinal cords were removed and a crude synaptosomal preparation obtained to examine mitochondrial function using the MTT assay, as well as measures of reactive oxygen species (ROS), lipid peroxidation, and glutamate and glucose uptake. ⋯ Neither drug treatment had an effect on glutamate or glucose uptake, both of which are reduced at acute times following SCI. Previous studies have documented that drugs acting on non-N-methyl-D-aspartate (NMDA) receptors exhibit greater efficacy compared to NMDA receptor antagonists on recovery of function and tissue sparing following traumatic spinal cord injury. The results of this study provide a potential mechanism by which blockade of the non-NMDA ionotropic receptors exhibit positive effects following traumatic SCI.
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Journal of neurotrauma · Aug 2002
Association between cerebrospinal fluid interleukin-6 concentrations and outcome after severe human traumatic brain injury.
Acute inflammation plays a significant role in the pathophysiology of traumatic brain injury (TBI). However, the specific relationships between inflammatory mediators and patient outcome following TBI have not been fully established. In this study, we measured plasma and cerebrospinal fluid interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations in 36 patients, following severe TBI. ⋯ Multiple regression analysis identified that age (p = 0.0072), pupillary abnormality (p = 0.021), the presence of mass lesion (p = 0.023), and peak CSF IL-6 concentrations (p = 0.026) were all statistically significant predictors of clinical outcome following TBI. These results suggest that peak CSF IL-6 concentrations correlate with improved outcome following TBI. This finding helps to characterize the inflammatory reaction associated with TBI and may help to develop improved treatment strategies for patients with TBI.
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Journal of neurotrauma · Aug 2002
Relationship between NOC/oFQ, dynorphin, and COX-2 activation in impaired NMDA cerebrovasodilation after brain injury.
Previous studies have observed that the recently described endogenous opioid, nociceptin/orphanin FQ (NOC/oFQ), contributes to impairment of N-methyl-D-aspartate (NMDA)-induced cerebrovasodilation following fluid percussion brain injury (FPI) via a cyclooxygenase (COX)-dependent generation of superoxide anion (O(2)(-)). This study was designed to investigate the relationship between NOC/oFQ, another opioid, dynorphin, and activation of the COX-2 isoform of the enzyme in such impaired dilation to NMDA after FPI in piglets equipped with a closed cranial window. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O(-)(2) generation. ⋯ These data also show that dynorphin contributes to O(2)(-) generation after FPI via COX-2 activation. These data additionally indicate that dynorphin and COX-2 activation contribute to impairment of NMDA pial artery dilation after FPI. Finally, these data suggest that NOC/oFQ impairs NMDA dilation postinsult via the sequential release of dynorphin, activation of COX-2, and generation of O(2)(-).
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Journal of neurotrauma · Jul 2002
Comparative StudyOutcome of traumatic brain injuries in 1,508 patients: impact of prehospital care.
This article describes the outcome of 1,508 patients with traumatic brain injuries (TBI) treated in a single neurosurgical unit over an 8-year period. Our aim has been to compare those outcomes with our previous results and with other large patient series. Another important goal was to evaluate the effect of the introduction of a 4-year ongoing study initiated in January 1993 using a new strategy of prehospital care on postresuscitation Glasgow Coma Score (GCS) and Glasgow Outcome Score (GOS). ⋯ For patients with GCS 3-4, an increased expected odds/ratio (2.0; p < 0.05) for a GOS 2-3 rather than a GOS 1 was seen. The principal conclusion is that outcome for the severely injured patients in the present study is more favorable than in other large series of TBI. We posit that the introduction of effective prehospital care most likely contributed to the improved postresuscitation neurological status and consequently to the better outcome observed after January 1993.
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Journal of neurotrauma · Jul 2002
Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats.
Traumatic brain injury (TBI) triggers a complex pathophysiological cascade, leading to cell death. A major factor in the pathogenesis of TBI is neuronal overloading with calcium, causing the opening of mitochondrial permeability transition pores (MPTP), which consequently inhibit normal mitochondrial function. The immunosuppressant Cyclosporin A (CsA) has been shown to block MPTPs, and to be neuroprotective in ischemia and TBI. ⋯ Furthermore, the lower dose of CsA also ameliorated acute motor deficits (days 1-5 post-FPI) and learning and memory impairments in a Morris water maze test on days 11-15 post-FPI. Although, the higher dose of CsA improved cognitive performance, it worsened acute motor functional recovery. These results suggest, that the CsA-induced preservation of mitochondrial function, as assessed by tissue O(2) consumption, directly translated into improvements in motor and cognitive behavior.