Rosuvastatin in Experimental Brain Trauma: Improved Capillary Patency but no Effect on Edema or Cerebral Blood Flow.
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BACKGROUND: Microvascular dysfunction, characterized by edema formation secondary to increased blood-brain barrier (BBB) permeability and decreased blood flow, contributes to poor outcome following brain trauma. Recent studies have indicated that statins may counteract edema formation following brain trauma but little is known about other circulatory effects of statins in this setting. The objective of this study was to investigate whether statin treatment improves brain microcirculation early after traumatic brain injury, and whether microvascular effects are associated with altered production of nitric oxide and prostacyclin. METHODS: After fluid percussion injury, rats were randomized to intravenous treatment with 20mg/kg of rosuvastatin or vehicle. Brain edema (wet/dry weight), BBB integrity ((51)Cr-EDTA blood to brain transfer), cerebral blood flow ((14)C-iodoantipyrine autoradiography), and number of perfused cortical capillaries (FITC-albumin fluorescence microscopy), were measured at 4 and 24hours. NO and prostacyclin production was estimated from plasma concentration of the degradation products NO2- and NO3- (NOx) and 6-keto-PGF1-alpha, respectively. Sham injured animals were treated with vehicle and analyzed at 4hours. RESULTS: Trauma resulted in brain edema, BBB dysfunction, and reduced cortical blood flow, with no effect of statin treatment. Trauma also induced a reduction in the number of perfused capillaries, which was improved by statin treatment. Statin treatment led to increased NOx levels and reduced mean arterial blood pressure. 6-keto-PGF1-alpha levels tended to increase after trauma, and were significantly reduced by rosuvastatin. CONCLUSIONS: Rosuvastatin treatment may improve microcirculation after traumatic brain injury by preserved patency of cerebral capillaries. This effect is associated with increased NO and reduced prostacyclin production. No effect on brain edema or BBB-barrier integrity was found.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Publication status||Published - 2013|