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General anesthetic exposure in adolescent rats causes persistent maladaptations in cognitive and affective behaviors and neuroplasticity.

Abstract：

:Accumulating evidence indicates that exposure to general anesthetics during infancy and childhood can cause persistent cognitive impairment, alterations in synaptic plasticity, and, to a lesser extent, increased incidence of behavioral disorders. Unfortunately, the developmental parameters of susceptibility to general anesthetics are not well understood. Adolescence is a critical developmental period wherein multiple late developing brain regions may also be vulnerable to enduring general anesthetic effects. Given the breadth of the adolescent age span, this group potentially represents millions more individuals than those exposed during early childhood. In this study, isoflurane exposure within a well-characterized adolescent period in Sprague-Dawley rats elicited immediate and persistent anxiety- and impulsive-like responding, as well as delayed cognitive impairment into adulthood. These behavioral abnormalities were paralleled by atypical dendritic spine morphology in the prefrontal cortex (PFC) and hippocampus (HPC), suggesting delayed anatomical maturation, and shifts in inhibitory function that suggest hypermaturation of extrasynaptic GABAA receptor inhibition. Preventing this hypermaturation of extrasynaptic GABAA receptor-mediated function in the PFC selectively reversed enhanced impulsivity resulting from adolescent isoflurane exposure. Taken together, these data demonstrate that the developmental window for susceptibility to enduring untoward effects of general anesthetics may be much longer than previously appreciated, and those effects may include affective behaviors in addition to cognition.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Landin JD,Palac M,Carter JM,Dzumaga Y,Santerre-Anderson JL,Fernandez GM,Savage LM,Varlinskaya EI,Spear LP,Moore SD,Swartzwelder HS,Fleming RL,Werner DF

doi

10.1016/j.neuropharm.2019.03.022

subject

Has Abstract

pub_date

2019-05-15 00:00:00

pages

153-163

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(18)30520-3

journal_volume

150

pub_type

杂志文章

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