Neuroprotective effect of atorvastatin in an experimental model of nerve crush injury.
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-kappaB and the elevated activation of c-Jun N-terminal kinase, Smad2/3, and activating protein-1 were associated with the neuroprotective action of atorvastatin.


CONCLUSIONS
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.
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan.
Hung-Chuan
HC
Pan
Dar-Yu
DY
Yang
Yen-Chuan
YC
Ou
Shu-Peng
SP
Ho
Fu-Chou
FC
Cheng
Chun-Jung
CJ
Chen
D000818:Animals; D000069059:Atorvastatin; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002463:Cell Membrane Permeability; D003094:Collagen / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000188:drug therapy; D009416:Nerve Regeneration / Q000187:drug effects; D018696:Neuroprotective Agents; D009195:Peroxidase / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D011758:Pyrroles; D003094:Collagen; D000069059:Atorvastatin; D009195:Peroxidase; D020169:Caspases