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.
Pan
Hung-Chuan
HC
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan.
Yang
Dar-Yu
DY
Ou
Yen-Chuan
YC
Ho
Shu-Peng
SP
Cheng
Fu-Chou
FC
Chen
Chun-Jung
CJ
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