Journal of neurotrauma
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Journal of neurotrauma · Jun 1999
Neuroprotective effect of hypothermia on neuronal injury in diffuse traumatic brain injury coupled with hypoxia and hypotension.
It is well established in mechanical head trauma that posttraumatic secondary insults, such as hypoxia and hypotension exacerbate neuronal injury and lead to worse outcome. In this study, the neuroprotective effect of hypothermia on the reduction of supraventricular subcortical neuronal damage was evaluated using an impact-acceleration model of diffuse traumatic brain injury coupled with both moderate and severe periods of hypoxia and hypotension. A total of 135 adult male Sprague-Dawley rats (340-375 g) were divided into three experimental studies: (I) physiological evaluation (n = 36); (II) quantitative analysis of the effect of trauma coupled with moderate and severe hypotension on neuronal damage assessed at 4 (n = 39) and 24 h (n = 24); and (III) the neuroprotective effect of hypothermia following moderate secondary insult (n = 36). ⋯ However, hypothermia provided nearly complete protection against secondary insults, and neuronal damage was equal to that of the trauma alone group (p = 0.42). The results of this study confirm that hypothermia provides remarkable protection against the adverse effects of neuronal damage exacerbated by secondary injury. This study also presents a new model of secondary insult, which can be used experimentally to further define the mechanism of increased vulnerability of the injured brain.
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Journal of neurotrauma · Jun 1999
Randomized Controlled Trial Multicenter Study Clinical TrialEffects of the bradykinin antagonist Bradycor (deltibant, CP-1027) in severe traumatic brain injury: results of a multi-center, randomized, placebo-controlled trial. American Brain Injury Consortium Study Group.
A phase II prospective, randomized, double blind clinical trial of Bradycor, a bradykinin antagonist, was conducted at 31 centers within North America in severely brain injured patients. Patients of Glasgow Coma Score (GCS) 3-8 (n = 139) with at least one reactive pupil were randomized to receive either Bradycor, 3 microg/kg/min or placebo as a continuous intravenous infusion for 5 days, with the infusion beginning within 12 h of the injury. The primary objective was to assess the efficacy of a continuous infusion of Bradycor (3.0 mc/kg/min) in preventing elevation of intracranial pressure (ICP). ⋯ There were fewer deaths in the Bradycor group, which had a 28-day all cause mortality of 20% versus 27% on placebo. Patients treated with Bradycor showed a 10.3% improvement in favorable outcome at 3 months and a 12% improvement in dichotomized GOS at 6 months (p = 0.26). The consistent positive trends seen in ICP, TIL, neuropsychological tests, and, most importantly, 3- and 6-month GOS provide supportive evidence that a bradykinin antagonist may play a neuroprotective role in severe brain injury.
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Journal of neurotrauma · Jun 1999
Severity of experimental brain injury on lactate and free fatty acid accumulation and Evans blue extravasation in the rat cortex and hippocampus.
Lactate and free fatty acids (FFAs) were extracted from the cortices and hippocampi of rats subjected to sham operation, or mild (1.25 atm) or moderate (2.0 atm) fluid percussion (FP) injury, and their total tissue concentrations were measured. The elevation of lactate in the injured left cortex (IC) and ipsilateral hippocampus (IH) was significantly greater in the moderate-injury than in the mild-injury group at most test times between 5 min and 48 h after injury. Levels of total FFAs were elevated in the IC and IH to a greater extent and for a longer period after injury in the moderate-injury (up to 48 h) than in the mild-injury group (up to 20 min). ⋯ The extravasation of Evans blue in the IC and IH from 3 to 6 h after injury was also the greatest in the moderate-injury group. The hippocampal CA3 neuronal cell loss, but not cortical lesion volume, also increased with the severity of injury. These findings suggest that certain neurochemical, physiological (blood-brain barrier permeability), and morphologic responses increase with the severity of FP brain injury, and such relationships are consistent with the increased behavioral deficits observed with the increase of severity of brain injury.
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Journal of neurotrauma · May 1999
Neuroprotective effects of basic fibroblast growth factor following spinal cord contusion injury in the rat.
Cytokines and neurotrophic factors have been implicated in the pathophysiology of injury to the central nervous system. While some cytokines are considered pro-inflammatory, other factors promote neuronal growth and survival. The present study investigated the neuroprotective effects of interleukins 1 (IL-1), 4 (IL-4), and 6 (IL-6), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF) in a contusion model of spinal cord injury. ⋯ No significant differences were observed between animals receiving vehicle versus bFGF treatment commencing 3 h after injury. These data demonstrate that the continuous intramedullary infusion of bFGF initiated one hour after moderate contusion injury of the spinal cord significantly reduces the total zone of injury and the zone of partial preservation. These results support the further investigation and possible future clinical application of bFGF in the treatment of acute spinal cord contusion injury.
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Journal of neurotrauma · May 1999
Behavioral responses of C57BL/6, FVB/N, and 129/SvEMS mouse strains to traumatic brain injury: implications for gene targeting approaches to neurotrauma.
Recent studies have suggested that mouse models of traumatic brain injury may be useful for evaluating the role of single gene products in brain trauma. In the present study, we report that three background strains (C57BL/6, FVB/N, and 129/SvEMS), commonly used in genetically altered mice, exhibit significantly different behavioral responses when subjected to sham surgery (n = 9 per group) or moderate controlled cortical impact (CCI) injury (n = 12 per group). Injured animals from all three strains showed delayed recovery of pedal withdrawal and righting reflexes compared to sham-operated controls. ⋯ Significant impairment of place learning in the Morris water maze and Barnes circular maze was observed at 7-10 days and 21-24 days after injury, respectively, in C57BL/6 mice when compared with sham controls. Sham-operated FVB/N and 129/SvEMS mice were unable to learn either task, and performance did not differ significantly from respective CCI injured animals. Our results suggest that background strain should be carefully considered with experiments involving genetically altered mice, especially when planning behavioral outcome measures after CNS injury.