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標題: Neuroprotective Effect of Atorvastatin in an Experimental Model of Nerve Crush Injury
作者: Pan, H.C.
Yang, D.Y.
Ou, Y.C.
Ho, S.P.
Cheng, F.C.
Chen, C.J.
關鍵字: Degeneration;Neuroprotection;Regeneration;Sciatic nerve;Statin;ischemia-reperfusion injury;nitric-oxide synthase;experimental;diabetic-neuropathy;traumatic brain-injury;nf-kappa-b;peripheral-nerve;sciatic-nerve;axonal regeneration;adult rats;matrix;metalloproteinases
Project: Neurosurgery
期刊/報告no:: Neurosurgery, Volume 67, Issue 2, Page(s) 376-388.
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.
ISSN: 0148-396X
DOI: 10.1227/01.neu.0000371729.47895.a0
Appears in Collections:獸醫學系所

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