title: Absence of Neuropathology With Prolonged Isoflurane Sedation in Healthy Adult Rats.
abstract: BACKGROUND
  The use of isoflurane sedation for prolonged periods in the critical care environment is increasing. However, isoflurane-mediated neurotoxicity has been widely reported. The goal of the present study was to determine whether long-term exposure to low-dose isoflurane in mechanically ventilated rodents is associated with evidence of neurodegeneration or neuroinflammation.
  
  
  METHODS
  Adult female Sprague-Dawley rats were used in this study. Experimental animals (n=11) were induced with 1.5% isoflurane, intubated, and given a neuromuscular blockade with α-cobratoxin. EEG electrodes were surgically implanted, subcutaneous precordial EKG Ag wire electrodes, and bladder, femoral artery, and femoral vein cannulas permanently placed. After these procedures, the isoflurane concentration was reduced to 0.5% and, in conjunction with the neuromuscular blockade, continued for 7 days. Arterial blood gases and chemistry were measured at 3 time points and core body temperature servoregulated and maintenance IV fluids were given during the 7 days. Experimental animals and untreated controls (n=9) were euthanized on day 7.
  
  
  RESULTS
  Immunohistochemical and cytochemical assays did not detect evidence of microgliosis, astrocytosis, neuronal apoptosis or necrosis, amyloidosis, or phosphorylated-tau accumulation. Blood glucose levels were significantly reduced on days 3/4 and 6/7 and partial pressure of oxygen was significantly reduced, but still within the normal range, on day 6/7. All other blood measurements were unchanged.
  
  
  CONCLUSIONS
  No neuropathologic changes consistent with neurotoxicity were detected in the brain after 1 week of continuous exposure to 0.5% isoflurane in healthy rats. These data suggest that even long exposures to low concentrations of isoflurane have no overt consequences on neuropathology.
authors.affiliation: *Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia †Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia ‡Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: DeYoung
authors.forename: John C
authors.initials: JC
authors.lastname: Li
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Tang
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Ward
authors.forename: Barry R
authors.initials: BR
authors.lastname: Dworkin
authors.forename: Maryellen F
authors.initials: MF
authors.lastname: Eckenhoff
authors.forename: William A
authors.initials: WA
authors.lastname: Kofke
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D016292:Procedural Sedation / Q000009:adverse effects*; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D007530:Isoflurane / Q000009:adverse effects*; D009336:Necrosis; D009443:Neuritis / Q000139:chemically induced / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D001786:Blood Glucose; D007530:Isoflurane