Articles: brain-injuries.
-
Retracted Publication
Kynurenate attenuates the accumulation of diacylglycerol and free fatty acids after experimental brain injury in the rat.
This study examined the effects of the administration of kynurenate, a non-specific excitatory amino acid (EAA) receptor subtype antagonist, on the regional accumulation of diacylglycerol (DG) and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. After brain injury of moderate severity (2.0 atm), rats were treated with either kynurenate (200 mg/kg, i.v.) or saline at 5 min after injury. In the saline-treated brain-injured rats, levels of all individual DG-fatty acids (palmitic, stearic, oleic and arachidonic acids) and total DG-fatty acids were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. ⋯ Kynurenate administration attenuated increases of all individual and total FFAs in the ipsilateral cortex and hippocampus either at 30 min alone or at both 30 min and 60 min after FP brain injury. In the contralateral cortex, levels of both DG-fatty acids and FFAs were not increased in the saline-treated injured rats and were also not affected by the administration of kynurenate. These results support the role of EAA receptor subtypes in the phospholipases-catalyzed formation of DG and FFAs in the ipsilateral cortex and hippocampus after lateral FP brain injury.
-
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.
-
Journal of neurotrauma · Jun 1999
Postinjury cyclosporin A administration limits axonal damage and disconnection in traumatic brain injury.
Recent observations concerning presumed calcium-induced mitochondrial damage and focal intraaxonal proteolysis in the pathogenesis of traumatic axonal injury (TAI) have opened new perspectives for therapeutic intervention. Studies from our laboratory demonstrated that cyclosporin A (CsA), a potent inhibitor of Ca2+-induced mitochondrial damage, administered 30 min prior to traumatic brain injury preserved mitochondrial integrity in those axonal foci destined to undergo delayed disconnection. We attributed this neuroprotection to the inhibition by CsA of mitochondrial permeability transition (MPT). ⋯ These results once again suggest that the maintenance of the functional integrity of the mitochondria can prevent TAI, presumably via the preservation of the local energy homeostasis of the axon. Moreover and perhaps more importantly, these studies also demonstrate the efficacy of CsA administration when given in the early posttraumatic period. Collectively, our findings suggest that a therapeutic window exists for the use of drugs targeting mitochondria and energy regulation in traumatic brain injury.
-
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.
-
The possible role of the polyamine interconversion pathway on edema formation, traumatic injury volume, and tissue polyamine levels after traumatic brain injury (TBI) was studied using an inhibitor of the interconversion pathway enzyme, polyamine oxidase. ⋯ These results demonstrate, for the first time, that the polyamine interconversion pathway has an important role in the increase of putrescine levels after TBI and that the polyamine oxidase inhibitors, blockers of the interconversion pathway, can be neuroprotective against edema formation and necrotic cavitation after TBI.