Impact of anesthesia exposure in early development on learning and sensory functions

Abstract

Each year, millions of children undergo anesthesia, and both human and animal studies have indicated that exposure to anesthesia at an early age can lead to neuronal damage and learning deficiency. However, disorders of sensory functions were not reported in children or animals exposed to anesthesia during infancy, which is surprising, given the significant amount of damage to brain tissue reported in many animal studies. In this review, we discuss the relationship between the systems in the brain that mediate sensory input, spatial learning, and classical conditioning, and how these systems could be affected during anesthesia exposure. Based on previous reports, we conclude that anesthesia can induce structural, functional, and compensatory changes in both sensory and learning systems. Changes in myelination following anesthesia exposure were observed as well as the neurodegeneration in the gray matter across variety of brain regions. Disproportionate cell death between excitatory and inhibitory cells induced by anesthesia exposure can lead to a long‐term shift in the excitatory/inhibitory balance, which affects both learning‐specific networks and sensory systems. Anesthesia may directly affect synaptic plasticity which is especially critical to learning acquisition. However, sensory systems appear to have better ability to compensate for damage than learning‐specific networks.

Effects of neonatal isoflurane anesthesia exposure on learning-specific and sensory systems in adults

“…However, as conditioned responses (CRs) were not completely abolished, the damage only partially disrupted learning-related pathways. Such deficits in learning reflect the cumulative impact of anesthesia-related damage as well as subsequent development and compensation by the brain 25 . In order to understand the nature of this damage, we used a number of MRI techniques to examine changes in key structures of the circuitry underlying trace ECC.…”

Propofol inhibits the expression of Abelson nonreceptor tyrosine kinase without affecting learning or memory function in neonatal rats

“…An increasing number of findings in animal models and cell culture studies have demonstrated that propofol can induce developmental neurotoxicity, raising serious concerns regarding the safety of pediatric propofol anesthesia (McInnis et al, 2002;Wang et al, 2000Wang et al, , 2010. The extent of this brain damage depends on the duration of anesthesia, the frequency of anesthesia exposure, and other factors related to the anesthesia protocol (Aksenov et al, 2020). Unfortunately, although many studies have found that propofol induces neurotoxicity in the developing animal brain, the specific mechanism of action remains largely unknown (Aksenov et al, 2020;Bosnjak et al, 2016;McInnis et al, 2002;Reitman & Flood, 2011;Wang et al, 2000Wang et al, , 2010.…”

“…The extent of this brain damage depends on the duration of anesthesia, the frequency of anesthesia exposure, and other factors related to the anesthesia protocol (Aksenov et al, 2020). Unfortunately, although many studies have found that propofol induces neurotoxicity in the developing animal brain, the specific mechanism of action remains largely unknown (Aksenov et al, 2020;Bosnjak et al, 2016;McInnis et al, 2002;Reitman & Flood, 2011;Wang et al, 2000Wang et al, , 2010.…”

“…Every year, millions of human newborns, infants, toddlers, and preschool‐aged children are exposed to anesthetic drugs due to the need for essential surgical or medical procedures (Reitman & Flood, 2011). Substantial evidence has indicated that general anesthetics can induce developmental neurotoxicity, including acute widespread neuronal cell death, followed by long‐term memory and learning abnormalities (Aksenov, Miller, Dixon, & Drobyshevsky, 2020; Bosnjak, Logan, Liu, & Bai, 2016; McInnis et al., 2002; Wang, Kaufmann, Sanchez‐Ross, & Johnson, 2000; Wang, Zhang, Liu, Paule, & Slikker, 2010). Propofol is one of the most commonly used intravenous drugs for the induction and maintenance of anesthesia and procedural and critical care sedation in children (Bosnjak et al., 2016).…”

Behavior and Regional Cortical BOLD Signal Fluctuations Are Altered in Adult Rabbits After Neonatal Volatile Anesthetic Exposure

“…Despite these previous reports of cellular injury in the cortex and thalamus, we found no difference in the magnitude and shape of the BOLD signal in the somatosensory cortex with whisker stimulation in either controls or anesthesiaexposed rabbits (Aksenov et al, 2016), which would indicate that the pathological effect of injury was not pronounced, at least on the functional level. A recent review (Aksenov et al, 2020a) concluded that the functions of the sensory systems are affected less by neonatal anesthesia than learning-related functions due to the stronger ability of the sensory system to compensate for significant structural damage. For example, the loss of 50% or more sensory fibers/neurons may not produce sensory deficiency.…”