Journal of neurotrauma
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Journal of neurotrauma · Oct 2001
Endothelin-Induced cyclooxygenase-dependent superoxide generation contributes to K+ channel functional impairment after brain injury.
This study determined if endothelin (ET-1) generates superoxide anion (O2-) in a cyclooxygenase-dependent manner and if such production contributes to impairment of dilation to activators of ATP-sensitive K+ (KATP) and calcium-sensitive K+ (Kca) channels following fluid percussion brain injury (FPI) in newborn pigs equipped with closed cranial windows. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O2- generation. Under non-brain injury conditions, topical ET-1 (10(-10) M, the concentration present in CSF following FPI) increased SOD-inhibitable NBT reduction from 1 +/- 1 to 17 +/- 3 pmol/mm2. ⋯ These data show that ET-1 increased O2- production in a cyclooxygenase-dependent manner and contributed to this production after FPI. These data also show that ET-1 blunted KATP and Kca channel-mediated cerebrovasodilation in a cyclooxygenase dependent manner. These data suggest that ET-1-induced cyclooxygenase-dependent O2- generation contributes to KATP and Kca channel function impairment after FPI.
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Journal of neurotrauma · Oct 2001
Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats.
Talampanel [(R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3] benzodiazepine] is an orally active noncompetitive antagonist of the AMPA subtype of glutamate excitatory amino acid receptors. The purpose of this study was to determine whether treatment with talampanel would protect in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, a fluid-percussion interface was positioned parasagittally over the right cerebral cortex. ⋯ In addition, treatment with talampanel starting at 30 min significantly attenuated neuronal damage in all three subsectors of the hippocampal CA1 sector compared to vehicle-treated rats (normal-neuron counts, right (ipsilateral) medial CA1: 80.3 +/- 2.0 [talampanel] vs. 66.3 +/- 2.1 [vehicle] (mean +/- SEM); middle CA1: 71.5 +/- 2.0 vs. 60.3 +/- 2.2; lateral CA1: 74.5 +/- 3.0 vs. 63.0 +/- 3.2, respectively). By contrast, when talampanel treatment was begun at 3 h, normal pyramidal-neuron counts were almost identical in both groups. Our findings document that talampanel therapy instituted 30 min after trauma significantly reduces histological damage.
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Journal of neurotrauma · Sep 2001
Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in infants and children.
Adrenomedullin is a recently discovered 52-amino acid peptide that is a potent vasodilator and is produced in the brain in experimental models of cerebral ischemia. Infusion of adrenomedullin increases regional cerebral blood flow and reduces infarct volume after vascular occlusion in rats, and thus may represent an endogenous neuroprotectant. Disturbances in cerebral blood flow (CBF), including hypoperfusion and hyperemia, frequently occur after severe traumatic brain injury (TBI) in infants and children. ⋯ CSF adrenomedullin was not significantly associated with other selected clinical variables. We conclude adrenomedullin is markedly increased in the CSF of infants and children early after severe TBI. We speculate that adrenomedullin participates in the regulation of CBF after severe TBI.
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Journal of neurotrauma · Sep 2001
Neuropsychological outcome in relation to the traumatic coma data bank classification of computed tomography imaging.
The Traumatic Coma Data Bank (TCDB) classification of CT (computed tomography) scan has been related to the general outcome and intracranial pressure evolution. Our aim was to analyse the relationship of this classification with neuropsychological outcome and late indices of ventricular dilatation. Fifty-seven patients with a moderate or severe head injury (mean admission Glasgow Coma Scale Score, 7.7) were studied from 122 consecutive cases. ⋯ Within the diffuse injury groups, the degree of diffuse damage was related to measures of verbal memory and attention and cognitive flexibility. Ventricular enlargement was more evident in patients with mass lesions and it decreased in the remaining groups as the severity of diffuse injury diminished. These results show that there is a relationship between acute intracranial lesion diagnosis according to TCDB classification and neuropsychological results and ventricular dilatation indices at 6 months postinjury.
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Journal of neurotrauma · Aug 2001
Comparative StudyStrain and model differences in behavioral outcomes after spinal cord injury in rat.
Spinal cord injury (SCI) results in loss of function below the level of injury and the development of chronic central pain (CCP) syndromes. Since different strains may develop and express chronic pain behaviors differently, we evaluated behavioral outcomes (locomotor recovery and the development of mechanical and thermal allodynia) in three commonly used strains of rats (Long-Evans, Wistar, and Sprague-Dawley) using two models of SCI. The two models examined were contusion at T10 (NYU impactor, 12.5 mm height) and the T13 hemisection. ⋯ Overall, the hemisection model produced a larger percentage of animals that developed CCP and had greater responses to mechanical stimulation. Thus, it appears that strain selection has a greater impact on locomotor recovery and model selection has a greater impact on the development of CCP following SCI. Furthermore, these results suggest that genetic factors may play a role in recovery following SCI.