Androgenic Modulation of the Chloride Transporter NKCC1 Contributes to Age-dependent Isoflurane Neurotoxicity in Male Rats

ConclusionsVulnerability to isoflurane neurotoxicity is abolished by blocking the androgen receptor, disrupting the function of NKCC1, or delaying the time of exposure to at least 2 weeks of age in male rats. These results support a dynamic role for androgens and chloride transporter proteins in perinatal anesthetic neurotoxicity.Editor ’s PerspectiveWhat We Already Know about This TopicExperimental data in laboratory animals suggest sex-dependent differences in neurocognitive and behavioral vulnerability to early life anesthesia exposureSteroid sex hormones play an important role in guiding sex-specific brain developmentThe relationship between steroid sex hormones and developmental anesthesia neurotoxicity is incompletely understoodWhat This Article Tells Us That Is NewBlockade of androgen receptors in 7-day-old male rats protects against isoflurane anesthesia-induced behavioral deficitsAndrogen receptor blockade results in a premature transition in the developmental expression profiles of chloride transporters NKCC1 and KCC2These observations suggest that regulation of specific chloride transporters, determining functional modalities of γ-aminobutyric acid–mediated neurotransmission, by androgens is a critical component for developmental anesthetic neurotoxicity

Source: Anesthesiology - June 25, 2020 Category: Anesthesiology Source Type: research