Pathophysiological Deficits in the Amygdala after Repeated Isoflurane Exposure


Name: Robert Long

Rank: MAJ

Organization: Henry M. Jackson Foundation for the Advancement of Military Medicine

Performance Site: Uniformed Service University of the Health Sciences, Bethesda, MD

Year Published: 2014

Abstract Status: Final


Service members wounded in combat operations, as well as civilians in need of multiple surgical interventions following trauma, may require multiple exposures to general anesthesia over a short period of time. There is a growing body of evidence that indicates that repeated exposure to general anesthesia leads to impairments in both humans and animals and induces postoperative cognitive dysfunction (POCD) in humans. The underlying mechanism is not clear, but may be linked to the ability of isoflurane anesthesia to alter neuronal excitability in the amygdala, a brain region critical for cognitve function and emotional regulation.

The long-term objective is to elucidate the mechanism by which isoflurane disrupts neuronal excitability. Design: male Sprague-Dawley rats 10 weeks old exposed to isoflurane anesthesia and rendered unconscious and immobile and divided into 3 major groups: sham control, single exposure, and repeated exposure and each exposure will last one hour. Repeated exposures will happen over one week with an interval of 48 hours between exposures. Our central hypothesis is that repeated isoflurane administration alters neuronal excitability and synaptic plasticity in the amygdala leading to long-lasting abnormalities in cognitive and behavioral function and emotional regulation of anxiety and depression. 

Our Specific Aims are: 

1. Aim #1 - To identify alterations in synaptic plasticity in the basalateral amygdala (BLA) at 1 day, 1 week and 1 month after repeated isoflurane anesthesia. I will perform field excitatory postsynaptic potential recordings to accomplish this aim in ex vivo briain slices. 

2. Aim #2 - To characterize the long-lasting alterations in GABAergic synaptic transmission and network excitability in the BLA, 1 month after repeated exposure to isoflurane. I will perform whole-cell recordings of GABAergic currents in the amygdala. 

3. Aim #3 - To characterize amygdala dependent behavioral deficits associated with repeated exposure to isoflurane. Depressive-like symptoms will be measured in Porsolt forced swim test and anxiety/locomotion will be measured in the open field test.


Final Report is available on NTRL: