Abstract
Traumatic brain injury (TBI) leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.
Highlights
Traumatic brain injury (TBI) remains one of the leading causes of death and disability in industrialized countries
We investigated the effect of acute and continuous treatment of simvastatin combining with vitamin C on behavior and inflammation in adult rats following experimental TBI
We have shown that treatment with vitamin C, simvastatin, or combination therapy could attenuate the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury and reduce neurological deficit after traumatic brain injury
Summary
Traumatic brain injury (TBI) remains one of the leading causes of death and disability in industrialized countries. Strategies that block inflammatory and oxidative mediators have been shown to induce neuroprotective and anti-inflammatory effects after brain injury [2]. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation and it has been comprehensively reviewed [3]. A class of lipid-lowering drugs, inhibit 3hydroxy-3-methylglutaryl-CoA reductase, thereby suppressing cholesterol biosynthesis. Apart from their lipid-lowering activities, statins have been shown to mediate pleiotropic effects in vitro and in vivo by reducing inflammation and oxidative stress [4, 5]. Several studies have shown that the administration of statins induced neuroprotective and antiinflammatory effects and improved neurological outcomes after experimental TBI [3, 6,7,8,9]
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