title: Mitochondrial protectant pramipexole prevents sex-specific long-term cognitive impairment from early anaesthesia exposure in rats.
abstract: BACKGROUND
  Exposure to general anaesthesia during critical stages of brain development results in long-lasting cognitive impairment. Co-administration of protective agents could minimize the detrimental effects of anaesthesia. Co-administration of R(+)pramipexole (PPX), a synthetic aminobenzothiazol derivative that restores mitochondrial integrity, prevents anaesthesia-induced mitochondrial and neuronal damage and prevents early development of cognitive impairment. Here, we determine the protective effects of PPX into late adulthood in male and female rats.
  
  
  METHODS
  Postnatal day 7 rats of both sexes were exposed to mock anaesthesia or combined midazolam, nitrous oxide, and isoflurane anaesthesia for 6 h with or without PPX. Cognitive abilities were assessed between 5 and 7 months of age using Morris water maze spatial navigation tasks.
  
  
  RESULTS
  Examination of spatial reference memory revealed that female, but not male, neonatal rats exposed to anaesthesia showed slowing of acquisition rates, which was significantly improved with PPX treatment. Examination of memory retention revealed that both male and female anaesthesia-treated rats have impaired memory retention performance compared with sham controls. Co-treatment with PPX resulted in improvement in memory retention in both sexes.
  
  
  CONCLUSIONS
  PPX provides long-lasting protection against cognitive impairment known to occur when very young animals are exposed to anaesthesia during the peak of brain development. Anaesthesia-induced cognitive impairment appears to be sex-specific with females being more vulnerable than males, suggesting that they could benefit more from early prevention.
authors.affiliation: Department of Anaesthesiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Boscolo
authors.forename: C
authors.initials: C
authors.lastname: Ori
authors.forename: J
authors.initials: J
authors.lastname: Bennett
authors.forename: B
authors.initials: B
authors.lastname: Wiltgen
authors.forename: V
authors.initials: V
authors.lastname: Jevtovic-Todorovic
mesh_terms: D018681:Anesthetics, General / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000627:therapeutic use; D052160:Benzothiazoles / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D000077487:Pramipexole; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
chemical_list: D018681:Anesthetics, General; D000975:Antioxidants; D052160:Benzothiazoles; D018696:Neuroprotective Agents; D000077487:Pramipexole
keywords: anaesthetics gases, nitrous oxide; anaesthetics volatile, isoflurane; memory; neonates; oxygen, toxicity; recovery, cognitive