Neuroprotective Effect of Atorvastatin in an Experimental Model of Nerve Crush Injury

Abstract

BACKGROUND: Statins have therapeutic benefits for the management of several disorders. A short-term course of a high-dose statin pretreatment has demonstrated neuroprotective effects against neurological diseases. However, the molecular basis underlying the neuroprotective action of statins remains unclear. OBJECTIVE: We investigated whether a short-term course of high-dose atorvastatin pretreatment has beneficial effects in protecting sciatic nerve from crush injury. METHODS: Atorvastatin (5 mg/kg) or saline was given orally to Sprague-Dawley rats for 7 days before injury. The rats were subjected to crush injury in the left sciatic nerve with a vessel clamp. Biochemical, functional, electrophysiological, and morphological alterations occurring during injury-induced degeneration/regeneration were examined. RESULTS: Atorvastatin improved injury-induced neurobehavioral/electrophysiological changes and axonal loss. Damage-associated alterations, including structural disruption, oxidative stress, inflammation, and apoptosis, were attenuated by atorvastatin. After injury, regeneration-associated genes, including growth-associated protein-43, myelin basic protein, ciliary neurotrophic factor, and collagen, were upregulated by atorvastatin. The suppression of extracellular signal-regulated kinase, AKT, signal transducer and activators of transcription-1, and necrosis factor-kappa B and the elevated activation of c-Jun N-terminal kinase, Smad2/3, and activating protein-1 were associated with the neuroprotective action of atorvastatin. CONCLUSION: These findings suggest that a short-term course of high-dose atorvastatin pretreatment can protect against sciatic nerve crush injury through modifying intracellular or extracellular environments, making it favorable for regeneration

Simvastatin Ameliorates Cauda Equina Compression Injury in a Rat Model of Lumbar Spinal Stenosis

“…7). The neuroprotective effect of simvastatin described with LSS animal model in the present study is consistent with recent reports witnessing the neuroprotection offered by statins in an experimental model of sciatic nerve crush injury (Pan et al 2010). …”

“…Although statins are mainly used to reduce cardiovascular morbidity and mortality through reducing cholesterol and low density lipoproteins levels (Igel et al 2002), recent studies have documented pleiotropic effects like anti-inflammatory, antiproliferative, antithrombic and antioxidant properties (Markovic-Plese et al 2008). Neuroprotective property of statins treatment were reported in animal models of neuroinflammatory SCI (Han et al 2011; Eroglu et al 2010; Pannu et al 2007; Pannu et al 2005), TBI (Abrahamson et al 2009; Li et al 2009; Wu et al 2010; Chauhan and Gatto 2011) and sciatic nerve injury (Pan et al 2010). Different doses of statins ranging from 1 mg/kg to 20 mg/kg body weight were tested in previous reports.…”

Hypoxia/Reoxygenation Stress Signals an Increase in Organic Anion Transporting polypeptide 1a4 (Oatp1a4) at the Blood–Brain Barrier: Relevance to CNS Drug Delivery

“…35,36 Studies in an in vivo rodent model of subarachnoid hemorrhage showed that atorvastatin reduced brain caspase-3 activity and DNA fragmentation, suggesting an ability to attenuate neuronal apoptosis. 37,38 Statininduced neuroprotection has been reported in a concentration range between 100 nmol/L and 1 mmol/L within the CNS, while neuronal toxicity has only been reported at concentrations above 1 mmol/L. 39 We therefore sought to determine whether pretreatment with the commonly prescribed statin atorvastatin could attenuate neuronal damage induced by H/R insult in our global oxygen deprivation model.…”

Tetramethylpyrazine inhibits neutrophil activation following permanent cerebral ischemia in rats

“…Some of the plasma samples were kept at À70 C until use. Neutrophils were purified by dextran sedimentation, then centrifuged through Ficoll-Hypaque according to our previously reported protocols [21]. Analysis of neutrophil migration was performed with a modified 24-well Transwell after the cells were labeled with calcein AM.…”