Isoflurane Anesthesia Elicits Protein Pattern Changes in Rat Hippocampus

Abstract

Postoperative cognitive dysfunction (POCD) is a known phenomenon occurring after anesthesia with volatile anesthetics (VA), such as isoflurane. Recent reports suggest that VA interact with neurodegenerative disease-associated proteins including compounds with pathogenic relevance in Alzheimer disease (AD) and induce processes that may be linked to AD neuropathology. Unfortunately, our present understanding of the exact anesthetics' molecular mechanisms of action, their side effects on the brain, and their catenation with AD pathology is still limited. The present study analyzes the differential proteome of the hippocampus immediately after and 3 days after a 3-hour 1 minimal alveolar concentration isoflurane anesthesia in rats. Differential 2-dimensional electrophoresis, mass spectrometry, and functional network mapping were used to identify and functionally classify 12 different hippocampal proteins, which were significantly regulated after isoflurane anesthesia (6 up-regulated, 11 down-regulated with P<0.01). Induction of differential expression ranged from 0.05 (25-fold down-regulation) to 4.4 (4.4-fold up-regulation). Ten proteins were regulated immediately after and 7 proteins 3 days after isoflurane exposure. The proteome displays isoflurane-responsive protein candidates, which have also been shown to play a role in AD. They were grouped according to their key biologic activities, which showed that isoflurane affects selected biologic processes including synaptic plasticity, stress response, detoxification, and cytoskeleton in early and late recovery phases after anesthesia. These processes are also affected in AD. Results are discussed in view of AD, the toxicity mechanisms of isoflurane as well as the implications for our present understanding and conduction of clinical anesthesia.