Developmental disruption of brain tissue oxygen regulation and deficiency of learning after neonatal anesthesia exposure

PROJECT SUMMARY
Millions of children undergo general anesthesia each year, and animal and human studies have
indicated that exposure to anesthesia at an early age can impact neuronal development, leading
to behavioral and learning impairments that manifest later in childhood and adolescence.
However, little is known about the methods which can be used to evaluate these impairments.
Our preliminary and published data suggest that changes in regional resting state functional
MRI (rsfMRI) can reflect the status of local neuronal networks and can have a predictive value
for anesthesia-induced learning deficiency. Regional rsfMRI depends on the regulation of local
brain tissue oxygen. Based on published and preliminary data we hypothesize that brain tissue
oxygen and regional rsfMRI regulation are modulated by GABAergic neurons (interneurons) but
neonatal anesthesia disrupts the development of this modulation and produces a specific
signature on the rsfMRI signal. In Aim 1 we will determine the mechanisms responsible for
regional rsfMRI and brain tissue oxygen regulation under normal conditions and after neonatal
anesthesia exposure by using brain tissue oxygen, BOLD fMRI, electrophysiological recordings,
local pharmacological and optogenetic approach in adults. In Aim 2 we will determine how the
development of regional rsfMRI and brain tissue oxygen fluctuations is affected by neonatal
anesthesia exposure and find time points when rsfMRI can predict the future behavioral
deficiency. Behavioral tests, local rsfMRI, brain tissue oxygen, and neuronal activity will be
recorded in across multiple time points after neonatal anesthesia exposure and in the control
group. The results of the proposed work will provide a clear picture of how the regulation of
brain tissue oxygen is affected by neonatal anesthesia exposure and will offer strong
translational value of resting-state fMRI to predict learning deficiency.

Grant Number: 5R01GM112715-09
NIH Institute/Center: NIH
Principal Investigator: Daniil Aksenov