JOURNAL ARTICLE

Reduction of spinal cord ischemia/reperfusion injury with simvastatin in rats

Takeshi Saito, Masanori Tsuchida, Shino Umehara, Tatsuro Kohno, Hiroshi Yamamoto, Jun-ichi Hayashi
Anesthesia and Analgesia 2011, 113 (3): 565-71
21680858

BACKGROUND: Surgery of the thoracic or thoracoabdominal aorta may cause spinal cord ischemia and subsequent paraplegia. However, conventional strategies for preventing paraplegia due to spinal cord ischemia provide insufficient protection and cause additional side effects. We hypothesized that simvastatin, a drug recently shown to be neuroprotective against brain ischemia/reperfusion, would be neuroprotective in a rat spinal cord ischemia/reperfusion model.

METHODS: Rats were randomly assigned to simvastatin, vehicle, or sham-surgery (sham) groups (n = 6 per group). Simvastatin (10 mg/kg) or vehicle was administered subcutaneously once daily for 7 days before aortic balloon occlusion, and once at 24 hours after reperfusion. Spinal cord ischemia was induced by balloon inflation of a 2F Fogarty catheter in the thoracic aorta, and the proximal mean arterial blood pressure was maintained at 40 mm Hg for 12 minutes. The sham group received the same operation without inflation of the balloon. Ischemic injury was assessed by hindlimb motor function using the Motor Deficit Index score at 6 to 48 hours after ischemic reperfusion, and histological assessment of the spinal cord was performed 48 hours after reperfusion.

RESULTS: The Motor Deficit Index scores at 24 and 48 hours after reperfusion were significantly improved in the simvastatin group compared with the vehicle group (P = 0.021 and P = 0.023, respectively). Furthermore, there were significantly more normal motor neurons in the simvastatin group than in the vehicle group (P = 0.037). The percentage area of white matter vacuolation was significantly smaller in the simvastatin group than in the vehicle group (P = 0.030).

CONCLUSIONS: Simvastatin treatment can attenuate hindlimb motor dysfunction and histopathological changes in spinal cord ischemia/reperfusion injury in rats.

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