Year: 2017
Type: dissertation
Abstract: Anesthetics cause postanesthetic memory deficits in animal models, and similar deficits may contribute to postoperative delirium and cognitive dysfunction in patients. We previously showed using a mouse model that etomidate-induced persistent memory deficits result from increased tonic GABAA receptor-mediated inhibitory current in the hippocampus, through an astrocyte-mediated mechanism. However, the underlying mechanisms are uncertain. The aims of this study were to: 1) determine whether widely used anesthetic and sedative agents persistently increase tonic GABAA current; 2) determine whether human astrocytes mediate the increase, and 3) identify the underlying mechanisms. The results show that several GABAergic drugs persistently increase tonic current and human astrocytes release soluble factors that mediate etomidateâ s effect on tonic current. Furthermore, etomidate and sevoflurane act through astrocytic GABAA receptors to trigger a pro-inflammatory signaling pathway, which underlies the persistent increase in tonic current. These results increase the mechanistic understanding of postanesthetic memory deficits and delineate treatment targets.
Source: TSpace (University of Toronto)
Author: Kirusanthy Kaneshwaran
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2803134688