Acta neurochirurgica. Supplement
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Acta Neurochir. Suppl. · Jan 2008
The modulation of aquaporin-4 by using PKC-activator (phorbol myristate acetate) and V1a receptor antagonist (SR49059) following middle cerebral artery occlusion/reperfusion in the rat.
We have pursued the concept that traumatic brain edema is predominantly cellular and that water entry is modulated in part by aquaporins. Aquaporin-4 (AQP4) has been shown to play a significant role in cellular edema formation. Phorbol myristate acetate (PMA) is a potent PKC activator; purportedly involved in modulation of AQP4 activity. Alternatively, AQP4 may be regulated by arginine-vasopressin. Administration of the vasopressin antagonist (SR49059) reduced brain water content and sodium shift following MCAo. To investigate if edema formation is affected by the reduction of AQP4 expression, we utilized PMA and SR49059 following middle cerebral artery occlusion model (MCAo), and measured AQP4 expression by Western-Blot (WB) techniques. ⋯ These studies support the hypotheses that PMA and SR49059 may be useful in reducing cerebral water accumulation by modulating AQP4 expression and that pharmacological manipulation of AQP4 may emerge as a viable strategy for the reduction of fulminating edema following ischemic injury.
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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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Acta Neurochir. Suppl. · Jan 2008
Effect of increased intracranial pressure on cerebral vasospasm in SAH.
Increased ICP is common and might precipitate cerebral vasospasm (VSP)-induced ischemic events in aneurysmal SAH (ASAH).Our objective was to determine if there is an association between increased ICP and transcranial colour coded Doppler-angiographic VSP (TCCD-A VSP) in relation to delayed neurological deficit (DND) and poor outcome. ⋯ Increased ICP, not decreased CPP, was related to VSP. The combination of TCCD-A VSP and increased ICP was predictive of poor outcome. Management of acute ASAH should include reduction of increased ICP especially when there is concomitant TCCD-A VSP.
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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.