title: A peroxisome proliferator-activated receptor gamma agonist attenuates neurological deficits following spinal cord ischemia in rats.
abstract: OBJECTIVE
  Neuroprotective 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.
  
  
  METHODS
  Forty-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.
  
  
  RESULTS
  Compared 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.
  
  
  CONCLUSIONS
  PPARγ 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul, Korea.
authors.forename: Hyunchang
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, SMU-SNU Boramae Medical Center, Seoul, Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul, Korea.
authors.forename: Sanghon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul, Korea.
authors.forename: Sahngun Francis
authors.initials: SF
authors.lastname: Nahm
authors.affiliation: Department of Anesthesiology and Pain Medicine, SMU-SNU Boramae Medical Center, Seoul, Korea.
authors.forename: Sungwon
authors.initials: S
authors.lastname: Min
authors.affiliation: Department of Thoracic Surgery, Seoul National University Bundang Hospital, Seoul, Korea.
authors.forename: Cheong
authors.initials: C
authors.lastname: Lim
authors.affiliation: Department of Thoracic Surgery, Seoul National University Bundang Hospital, Seoul, Korea.
authors.forename: Kayhyun
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul, Korea. Electronic address: noninvasive@hanmail.net.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Han
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D004195:Disease Models, Animal; D007238:Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D008315:Malondialdehyde; D000077205:Pioglitazone