Journal of neurotrauma
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Journal of neurotrauma · Aug 1998
Effects of moderate, central fluid percussion traumatic brain injury on nitric oxide synthase activity in rats.
Experimental traumatic brain injury (TBI) damages cerebral vascular endothelium and reduces cerebral blood flow (CBF). The nitric oxide synthase (NOS) substrate, L-arginine, prevents CBF reductions after TBI, but the mechanism is not known. This study examined the possibility that post-traumatic hypoperfusion is due to reductions in the substrate sensitivity of NOS which are overcome by L-arginine. ⋯ Total cortical soluble NOS activity in TBI-treated rats was not significantly different from either untreated or sham groups when 0.45 microM or 1.5 microM L-arginine was added. Also, there were no differences in cell-dependent NOS activity among the three groups stimulated by 300 microM N-methyl-D-aspartate, 50 mM K+, or 10 microM ionomycin. These data suggest that TBI reduces CBF by a mechanism other than altering the substrate specificity or activation of nNOS.
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Journal of neurotrauma · Aug 1998
Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse.
A mouse model of traumatic brain injury was developed using a device that produces controlled cortical impact (CCI), permitting independent manipulation of tissue deformation and impact velocity. The left parietotemporal cortex was subjected to CCI [1 mm tissue deformation and 4.5 m/s tip velocity (mild), or 6.0 m/s (moderate)] or sham surgery. Injured animals showed delayed recovery of pedal withdrawal and righting reflexes compared to sham-operated controls. ⋯ Triple fluorescence labeling with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), antineuronal nuclear protein (NeuN), and Hoechst 33258 of parallel sections showed frequent apoptotic neurons. These findings demonstrate sustained and reproducible deficits in sensory/motor function and spatial learning in the CCI-injured mouse correlating with injury severity. Mechanisms of neuronal cell death after trauma as well as strategies for evaluating novel pharmacological treatment strategies may be identified using this model.
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Journal of neurotrauma · Jul 1998
Comparison of brain tissue oxygen tension to microdialysis-based measures of cerebral ischemia in fatally head-injured humans.
This study investigated the relationship between brain tissue oxygen tension (PbtO2) and cerebral microdialysate concentrations of several compounds in five patients with refractory intracranial hypertension after severe head injury. The following substances were assayed: lactate and glucose; the excitatory amino acids glutamate and aspartate; and the cations potassium, calcium, and magnesium. Glucose concentrations did not correlate with PbtO2, but lactate increased as PbtO2 decreased. ⋯ Calcium and magnesium concentrations did not vary in response to PbtO2. In summary, the most robust biochemical indicators of cerebral anoxia were elevations in the lactate/glucose ratio and in the concentrations of lactate and of the excitatory amino acids glutamate and aspartate. Furthermore, the fact that glucose concentrations continue to decrease for a short period after oxygen levels reach zero suggests that cells continue to utilize glucose anaerobically for such functions as maintenance of cellular integrity, with collapse of the cell membrane as evidenced by increases of extracellular glutamate and aspartate not occurring until both oxygen and glucose concentrations reach zero.
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Journal of neurotrauma · Jul 1998
Dynorphin mRNA expression in dorsal horn neurons after traumatic spinal cord injury: temporal and spatial analysis using in situ hybridization.
Dynorphin, an endogenous opioid, may contribute to secondary nervous tissue damage following spinal cord injury. The temporal and spatial distribution of preprodynorphin (PPD) mRNA expression in the injured rat spinal cord was examined by in situ hybridization. Rats were subjected to traumatic spinal cord injury at the T13 spinal segment using the weight-drop method. ⋯ The number of neurons expressing PPD mRNA in each rat was significantly positively correlated with its motor dysfunction. These findings suggest that increased expression of dynorphin mRNA and peptide in dorsal horn neurons occurs after traumatic spinal cord injury. This also supports the hypothesis that the dynorphin has a pathological role in secondary tissue damage and neurological dysfunction after spinal cord injury.
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Journal of neurotrauma · Jun 1998
Soluble ICAM-1 in CSF coincides with the extent of cerebral damage in patients with severe traumatic brain injury.
The intercellular adhesion molecule-1 (ICAM-1) expressed by endothelial cells is crucial in promoting adhesion and transmigration of circulating leukocytes across the blood-brain barrier (BBB). Migrated immunocompetent cells, in turn, release mediators that stimulate glial and endothelial cells to express ICAM-1 and release cytokines, possibly sustaining cerebral damage. Following activation, proteolytic cleavage of membrane-anchored ICAM-1 results in measurable levels of a soluble form, sICAM-1. ⋯ In addition, overall analysis showed that sICAM-1 in CSF correlated with the extent of BBB damage as indicated by the QA (r = 0.76; p < 0.001). These results suggest that increased sICAM-1 levels in CSF might depict ongoing immunologic activation and that sICAM-1 correlates with the extent of tissue and BBB damage. The origin of soluble ICAM-1 in CSF and its pathophysiologic role after TBI remains to be clarified.