Long-Term GABAergic Modulation of Brain Tissue Oxygenation and Electrophysiological Activity Following Neonatal Anesthesia Exposure.

Millions of children are exposed to general anesthesia annually, raising concerns about its impact on neuronal development, subsequent behavioral impairments, and the conditions under which these functional deficiencies can be detected instrumentally. In this study, we investigated the delayed consequences of administering sevoflurane, a widely used anesthetic, to newborn rabbits to mimic repeated clinical anesthesia exposure. When these rabbits reached adolescence/adulthood, we implanted electrodes into their cerebral cortex to record electrophysiology and tissue oxygen. Tissue oxygen recording was chosen to show translational changes in hemodynamics, which can be detected by functional MRI. Despite observing no differences in baseline oxygen between the group exposed to neonatal anesthesia and the control group, subsequent administration of GABA antagonists in small concentrations near the oxygen electrodes revealed significant findings. While the local administration of the GABA antagonist picrotoxin resulted in a noticeable shift in oxygen oscillations to lower frequencies in both groups, the rabbits exposed to neonatal anesthesia also generated large and sustained response curves associated with epileptic activity. This study suggests the specific effects of neonatal anesthesia in inducing a state of susceptibility to epileptic activity, which can be triggered by specific and mild challenges (e.g., the application of picrotoxin in small concentrations). We generalize these findings to suggest that this mechanism can explain the inconsistency of clinical manifestations in populations exposed to neonatal anesthesia, as the anesthesia alone may not be sufficient for clinical symptoms to appear; an additional trigger or challenge is required.