Beyond anesthetic properties: the effects of isoflurane on brain cell death, neurogenesis, and long-term...

Anesthetic drugs cause brain cell death and long-term neurocognitive dysfunction in neonatal rats. Recently, human data also suggest that anesthesia early in life may cause cognitive impairment. The connection between cell death and neurocognitive decline is uncertain. It is conceivable that mechanisms other than brain cell death contribute to neurocognitive outcome of neonatal anesthesia. In a series of experiments, we demonstrate that isoflurane exposure causes significant hypercarbia in postnatal day 7 rats and that exposure to isoflurane or carbon dioxide for 4 h provoked brain cell death. However, 1 h of isoflurane exposure was not sufficient to cause brain cell death. Moreover, only 4 h of isoflurane exposure, but not 1 or 2 h of exposure or 4 h of carbon dioxide, led to impaired hippocampal function,questioning the association between anesthesia-induced brain cell death and neurocognitive dysfunction. Neurogenesis both in the developing and adult dentate gyrus is important for hippocampal function, specifically learning and memory. γ-Amino-butyric-acid regulates proliferation and neuronal differentiation both in the developing and the adult brain. Inhaled anesthetics are γ-amino-butyric-acid-ergic and may therefore affect neurogenesis, which could be an alternative mechanism mediating anesthesia-induced neurocognitive decline in immature rats. Understanding the mechanism will help guide clinical trials aiming to define the scope of the problem in humans and may lead to preventive and therapeutic strategies.