Acta neurochirurgica. Supplement
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Acta Neurochir. Suppl. · Jan 2008
The antioxidant effects of melatonin after intracerebral hemorrhage in rats.
Free radical mechanisms are involved in secondary brain injury after intracerebral hemorrhage (ICH). Since melatonin is a potent free radical scavenger and indirect antioxidant, the objective of this study was to evaluate whether melatonin administration would attenuate oxidative stress, brain edema, and neurological deficits in a rat model of ICH. Animals were assigned into groups consisting of sham (needle trauma), vehicle, and melatonin (15 or 150 mg/kg). ⋯ Results demonstrated dramatically increased lipid peroxidation after collagenase-induced ICH; however, melatonin treatment effectively attenuated this lipid peroxidation. Nonetheless, neurological scoring and brain water content in the right basal ganglia was without significant difference between any treatment regimens (15 or 150 mg/kg of melatonin) or time points of drug administration (15 min or 3 h post-ICH). Therefore, melatonin reduced oxidative stress but did not change extent of brain edema or neurologic deficits.
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Acta Neurochir. Suppl. · Jan 2008
Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059, decreases trauma-induced brain edema.
Currently, there are no pharmacological treatments available for traumatically induced brain edema and the subsequent rise of ICP. Evidence indicates that Aquaporin-4 (AQP4) plays a significant role in the pathophysiology of brain edema. Previously we have reported that SR49059 reduced brain edema secondary to ischemia. We, therefore, examined whether the selective V1a receptor antagonist, SR49059, reduces brain edema by modulating AQP4 expression following cortical contusion injury (CCI). ⋯ SR49059 significantly reduced trauma-induced AQP4 up-regulation in the contused hemisphere. Moreover, brain water content was also significantly reduced paralleling the AQP4 suppression. These data provide further support that vasopressin (AVP) and V1a receptors can control water flux through astrocytic plasma membranes by regulating AQP4 expression. Taken in concert, these results affirm our laboratories contention that AQP4 can be effectively modulated pharmacologically.
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Approximately 15% of all strokes are due to intracerebral hemorrhage, and of these, 5 to 9% will occur in the pons, with mortality approximately 60% of the time. However, there is not an adequate animal model to fully address this important clinical problem. To this end, pontine hemorrhage was induced in rats using stereotaxic injection of 0.15 units of collagenase. ⋯ All tested parameters were significantly increased, compared to sham, without any differences between time points. Furthermore, the extent of brainstem edema was highly correlated with neurological score, inclined plane, and body temperature. This new pontine hemorrhage rat model demonstrated brain edema and neurological deficits, and can be used to test treatment strategies for pontine hemorrhage.
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Acta Neurochir. Suppl. · Jan 2008
Effect of amantadine sulphate on intracerebral hemorrhage-induced brain injury in rats.
Recent studies have shown that amantadine, an uncompetitive N-methyl-d-aspartate receptor antagonist and dopamine agonist, is effective for the treatment of various cerebral disorders and causes relatively mild side effects. In this study, we investigated whether administration of amantadine will provide a neuroprotective effect in the intracerebral hemorrhage (ICH) rat model. A total of 15 male Sprague Dawley rats (300-380 g) were divided into sham, ICH-untreated, and ICH-treated with amantadine sulphate groups. ⋯ Our data demonstrates that ICH caused significant neurological deficit associated with marked brain edema. Amantadine did not reduce brain injury after ICH; neurological function and brain edema in the treated group were not different from those of the untreated group. We conclude that amantadine sulphate does not offer neuroprotection in acute stage of experimental ICH-induced brain injury.
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Acta Neurochir. Suppl. · Jan 2008
Effects of superoxide dismutase and catalase derivates on intracerebral hemorrhage-induced brain injury in rats.
The use of exogenous superoxide dismutase (SOD) and catalase (CAT) has been previously evaluated against various reactive oxygen species-mediated brain injuries, especially those associated with ischemia/ reperfusion. In this study, we investigated effects of these enzymatic antioxidants on intracerebral hemorrhage (ICH)-induced brain injury. A total of 65 male Sprague-Dawley rats (300-380 g) were divided into a sham group, an untreated ICH group, 3 groups of ICH rats treated with lecithinized SOD (PC-SOD) at doses of 0.1, 0.3, and 1 mg/kg, and a group treated with polyethylene glycol conjugated CAT (PEG-CAT) at a dose of 10,000 U/kg. ⋯ Our results demonstrated that ICH caused significant neurological deficit associated with remarkable brain edema. Treatment with PC-SOD, PEG-CAT, or PC-SOD in combination with PEG-CAT did not reduce brain edema or neurological deficit after ICH. We conclude that intravenously administered PC-SOD and/or PEG-CAT do not reduce brain injury in the collagenase-induced ICH rat model.