title: 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.
authors.affiliation: From the *Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; †Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; ‡Division of Cardiovascular Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; §Department of Anesthesiology, Buddhist Tzu Chi General Hospital and Tzu Chi University School of Medicine, Hualien, Taiwan; and ‖Department of Anesthesiology, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Fang
authors.forename: Jung-Shun
authors.initials: JS
authors.lastname: Lee
authors.forename: Jun-Neng
authors.initials: JN
authors.lastname: Roan
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Tsai
authors.forename: Chen-Fuh
authors.initials: CF
authors.lastname: Lam
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C100745:Aif1 protein, rat; D018685:Anesthetics, Inhalation; D002135:Calcium-Binding Proteins; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D008840:Microfilament Proteins; D007530:Isoflurane; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3