Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Aug 2009
Randomized Controlled TrialBiologic effects of simvastatin in patients with aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled randomized trial.
Recently, two randomized controlled phase II studies showed that acute initiation of statin treatment directly after aneurysmal subarachnoid hemorrhage (SAH) decreases the incidence of radiologic vasospasm and clinical signs of delayed cerebral ischemia (DCI), and even reduces mortality. It was hypothesized that the beneficial effect resulted from pleiotropic effects of statins. The purpose of this study was to investigate the biologic effects of acute statin treatment in patients with SAH. ⋯ With regard to primary outcomes, there were significant differences by treatment group for total cholesterol and low-density lipoprotein (LDL) cholesterol (P<0.0001), but not for parameters of coagulation, fibrinolysis, endothelium function, and inflammation. With regard to secondary outcomes, no differences were observed in the incidence of transcranial Doppler vasospasm, clinical signs of DCI, and poor outcome. We conclude that both the primary and secondary outcome results of this study do not support a beneficial effect of simvastatin in patients with SAH.
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J. Cereb. Blood Flow Metab. · Aug 2009
Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury.
Brain edema and swelling is a critical factor in the high mortality and morbidity associated with traumatic brain injury (TBI). Despite this, the mechanisms associated with its development are poorly understood and interventions have not changed in over 30 years. Although neuropeptides and neurogenic inflammation have been implicated in peripheral edema formation, their role in the development of central nervous system edema after brain trauma has not been investigated. ⋯ Inhibition of SP action by administration of the neurokinin-1 (NK1) antagonist, N-acetyl-L-tryptophan, at 30 mins after trauma attenuated vascular permeability and edema formation. Administration of the NK1 antagonist also improved both motor and cognitive neurologic outcomes. These findings suggest that SP release is integrally linked to the increased vascular permeability and edema formation after brain trauma, and that treatment with an NK1 receptor antagonist reduces edema and improves neurologic outcome.