Effects Of Simvastatin On Microglial Responses In Spinal Cord And Nerve Regeneration After Sciatic Nerve Crush Injury In Rat

Background and Purpose:Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in cholesterol biosynthesis. Because of their ability to inhibit the synthesis of cholesterol, statins are widely used in medical practice as the main therapy for hypercholesterolemia. In addition to this effect, there is growing evidences to suggest that the non-cholesteroldependent effects of statins, so called pleiotropic effects, lead to neuroprotective effects in many CNS disorders such as stoke, Alzheimer disease, multiple sclerosis, and so on. Preclinical researches show that controlling the activity of Rho GTPases would be possible to promote nerve regeneration. Thus Statins may promote nerve regeneration and functional recovery through its pleiotropic effect. By far the most compelling evidence supporting a critical role of microglia in neuroprotection comes from observing the cells'natural response to acute axonal injury. Axotomy of motoneurons in the periphery triggers a microglial response almost immediately after the injury has occurred. The activation of microglia by injured motor neurons is an integral, and potentially crucial, component of this regeneration program. Therefore our experiment aimed at exploring the microglial responses and the nerve repair after Simvastatin used for sciatic nerve with crush injury in rat.Methods: 60 adult female Sprague-Dawley rats were randomized into the following experimental groups: Simvastatin-treated, vehicle- treated and sham-operated groups. The animal model of sciatic nerves crush injury were...