Atorvastatin prevents early apoptosis after thoracic spinal cord contusion injury and promotes locomotion recovery.
The systemic administration of atorvastatin has been shown to be neuroprotective after spinal cord injury (SCI), by decreasing the inflammatory response at the lesion site and by reducing neuronal and oligodendrocyte apoptosis. The latter effect spares white matter at the injury site and improves locomotion. The aim of this study was to confirm the neuroprotective efficacy of atorvastatin as well as its early action in limiting apoptosis with its administration post-SCI. Female Sprague-Dawley rats received an intra peritoneal injection of: (1) statin/saline (5mg/kg) at 2h after the contusion injury; (2) physiological saline at 2h post-SCI; or (3) physiological saline without injury. Statin-treated rats showed significant (p<0.05) improvement in locomotion at week 4 post-SCI compared to vehicle-treated animals. Explaining this outcome, caspase-3 activity decreased by 50% (p<0.05), and the histological TUNEL method revealed a decrease of approximately 20% in apoptotic cells at the injury site (p<0.01) at 4h post-SCI in atorvastatin-treated rats in comparison to vehicle-treated controls. These data demonstrate that atorvastatin is effective after experimental spinal cord contusion injury in preventing early apoptosis at the injury site within 2h post-administration.
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, Département de pharmacologie, Université de Montréal, Montréal, Québec, Canada.
Marc-André
MA
Déry
Guy
G
Rousseau
Mohamed
M
Benderdour
Eric
E
Beaumont
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D013904:Thoracic Vertebrae
D006538:Heptanoic Acids; D018696:Neuroprotective Agents; D011758:Pyrroles; D000069059:Atorvastatin; D053148:Caspase 3