A peroxisome proliferator-activated receptor gamma agonist attenuates neurological deficits following spinal cord ischemia in rats

ObjectiveNeuroprotective effects of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist in cerebral ischemia have been reported, but the effect of a PPARγ agonist on spinal cord ischemia has not been investigated. The objective of this study was to investigate the effect of a PPARγ agonist on spinal cord ischemia. Pioglitazone, a PPARγ agonist, was administered in a rat model of spinal cord ischemia, and the extent of neurological damage and histological alterations were assessed.MethodsForty-five rats were randomly enrolled into one of the three groups: (1) pioglitazone group (group PIO): rats were treated with pioglitazone 24 hours before ischemia; (2) control group (group C): rats were treated with the same volume of saline 24 hours before ischemia; and (3) sham group (group sham): rats were treated with the same volume of saline 24 hours before the sham surgery. Spinal cord ischemia was induced using a balloon-tipped catheter placed on the proximal descending aorta. Neurologic function was assessed using the motor deficit index (0 = normal, 6 = complete paralysis) during the 48 hours after reperfusion. Histological and biochemical evaluations were then performed.ResultsCompared with group C, group PIO presented with lower motor deficit index 48 hours after reperfusion (5.0 [4.0-6.0] vs 3.0 [2.0-3.0]; group C vs group PIO, respectively; P < .001). Group PIO presented with a higher number of normal motor neurons (10.7 [8.1-11.9] vs 14.7 [14.0-15.3]; group C vs group PIO, respectively; P = .009) and a smaller area of infarcts (48.4% [46.3%-54.0%] vs 16.8% [11.5%-18.3%]; group C vs group PIO, respectively; P = .009) when compared with group C. The degree of inflammatory reactions, assessed by microglia activities, was significantly reduced in group PIO. Oxidative stress level, assessed using malonydialdehyde assay, was significantly reduced in group PIO relative to group C (192.21% [173.5%-206.4%] of sham vs 141.1% [131.7%-152.1%] of sham; group C vs group PIO, respectively; P = .007). The sham group exhibited no abnormality upon neurological or histological examination.ConclusionsPPARγ agonist pioglitazone pretreatment significantly reduces infarct volume and attenuates neurological deficits following spinal cord ischemia. The possible mechanism of neuroprotection by PPARγ agonist may involve modulation of inflammatory reaction and oxidative stress.

Clinical RelevanceSpinal cord ischemia is a major issue in thoracoabdominal aortic surgery. The proliferator-activated receptor agonists have been reported to exert protective effects on ischemia in various organs including cerebral ischemia. This study investigated the effect of a proliferator-activated receptor gamma agonist pioglitazone on spinal cord ischemia in a rat model of spinal cord ischemia. Our results present a protective effect of pioglitazone pretreatment to attenuate spinal cord ischemic injury. Considering that pioglitazone is currently a U.S. Food and Drug Administration-approved agent for treatment of type 2 diabetes, it may be applied in clinical practice to attenuate spinal cord ischemia injury following thoracoabdominal aortic surgery.