Isoflurane Differentially Affects Neurogenesis and Long-term Neurocognitive Function in 60-day-old and 7-day-old Rats

Abstract

ANESTHESIA kills neonatal brain cells of several animal species, including primates.1 A combination of γ-aminobutyric-acid (GABA)–ergic and N -methyl-d-aspartate antagonist agents is particularly neurotoxic; however propofol, isoflurane, ketamine, and midazolam have all caused apoptosis individually.1 We have shown that 4 h of hypercapnia, which caused a similar degree and distribution of cell death as 4 h of isoflurane, did not cause a neurocognitive deficit.2 Likewise, 2 h of isoflurane caused cell death in many areas of the brain relevant to the behavioral outcome tested, but no neurocognitive deficit was observed.2 The only intervention that caused both cell death and neurocognitive dysfunction was 4 h of isoflurane. This raises suspicion about whether anesthesia-related brain cell death in postnatal day (P)7 rats can really account for the cognitive deficit observed after anesthesia.2–5