Acta neurochirurgica. Supplement
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Acta Neurochir. Suppl. · Jan 2008
Simvastatin attenuates cerebral vasospasm and improves outcomes by upregulation of PI3K/Akt pathway in a rat model of subarachnoid hemorrhage.
Cerebral vasospasm is a common sequelae of subarachonoid hemorrhage (SAH), however, the mechanism of cerebral vasospasm is still unclear. Recently, statins have been shown to have efficacy in ameliorating cerebral vasospasm. The present study investigates whether simvastatin attenuates cerebral vasospasm after subarachnoid hemorrhage (SAH) via upregulation of the PI3K/Akt pathway. ⋯ The beneficial effects of high dose simvastatin in ameliorating cerebral vasospasm are likely mediated by upregulation of the PI3K/Akt pathway.
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Acta Neurochir. Suppl. · Jan 2008
ReviewVasospasm after aneurysmal subarachnoid hemorrhage: need for further study.
Cerebral vasospasm is the classic cause of delayed neurological deterioration leading to cerebral ischemia and infarction, and thus, poor outcome and occasionally death, after aneurysmal subarachnoid hemorrhage (SAH). Advances in diagnosis and treatment, principally nimodipine, intensive care management, hemodynamic manipulations, and endovascular neuroradiology procedures, have improved the prospects for these patients, but outcomes remain disappointing. A phase 2b clinical trial (CONSCIOUS-1) demonstrated marked prevention of vasospasm with the endothelin antagonist, clazosentan, yet patient outcome was not improved. ⋯ Clazosentan reduced angiographic vasospasm in a dose-dependent manner in patients with aneurysmal SAH following coiling or clipping of the aneurysm. Reducing the incidence of vasospasm should have an important effect on clinical outcome. A phase 3 clinical trial (CONSCIOUS-2) will focus on quantifying this outcome in patients undergoing aneurysm clipping receiving placebo or 5 mg/h of clazosentan.
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Intracerebral hemorrhage (ICH) is a subtype of stroke with very high mortality. Experiments have indicated that clot lysis and iron play an important role in ICH-induced brain injury. Iron overload occurs in the brain after ICH in rats. ⋯ Deferoxamine can rapidly penetrate the blood-brain barrier and accumulate in the brain tissue in significant concentration after systemic administration. We have demonstrated that deferoxamine reduces ICH-induced brain edema, neuronal death, brain atrophy, and neurological deficits. Iron chelation with deferoxamine could be a new therapy for ICH.
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Acta Neurochir. Suppl. · Jan 2008
Randomized Controlled Trial Clinical TrialPreliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial.
Compared to ischemic stroke, intracerebral hemorrhage (ICH) is easily and rapidly identified, occurs in younger patients, and produces relatively small initial injury to cerebral tissues--all factors suggesting that interventional amelioration is possible. Investigations from the last decade established that extent of ICH-mediated brain injury relates directly to blood clot volume and duration of blood exposure to brain tissue. Using minimally-invasive surgery plus recombinant tissue plasminogen activator (rtPA), MISTIE investigators explored aggressive avenues to treat ICH. ⋯ There is tentative indication that minimally-invasive surgery plus rtPA shows greater clot resolution than traditional medical management.