Isoflurane Impairs Motor Function Recovery by Increasing Neuroapoptosis and Degeneration During Spinal Ischemia-Reperfusion Injury in Rats.

Abstract

Spinal cord ischemia (SCI) leads to variable degrees of neurologic deficit in patients undergoing major cardiovascular surgery. The effect of intraoperative neuroprotection against SCI and the subsequent ischemia-reperfusion injury is still limited. Because isoflurane is a commonly used anesthetic agent during major operation, and its neuroprotective and neurotoxicity effects have both been discussed, this study aimed to investigate the effect of isoflurane on the spinal cord's functional recovery in a rat model of cord ischemia. Rats were randomly anesthetized by parenteral anesthetic (Zoletil) and isoflurane (0% and 1.5% v/v in oxygen). Cord ischemia was induced by cross-clamping of thoracic aorta at the level of T5, and cord perfusion was resumed after 25 minutes. The motor function was assessed independently up to 48 hours after reperfusion. Spinal cords were harvested and analyzed for molecular and histologic changes. The locomotor rating scale was significantly reduced in rats that received isoflurane treatment during SCI at 12 to 48 hours after reperfusion. Isoflurane enhanced the expression of heme oxygenase-1, glial fibrillary acidic protein, cleaved caspase-3, and Iba-1 in the spinal cord. Increased apoptotic cells and the presence of axonal damage were also observed in the histologic sections. Our results demonstrate that the administration of inhaled isoflurane in spinal cord ischemia-reperfusion injury impairs the recovery of motor function. This response is associated with the neuronal apoptosis and degeneration. This study highlights the potential adverse effect of isoflurane on the functional recovery of ischemic spinal cord during major aortic surgery.