Is the elderly brain susceptible to potential neurotoxic effects of inhalational anesthetics? Clinical studies are inconclusive, but isoflurane can induce the accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and decrease in ATP values, which may result in caspase-3 activation. This protease enzyme cleaves amyloid precursor protein, causing the oligomerization and accumulation of beta-amyloid protein associated with learning and memory impairment.
Dr. Zhongcong Xie, Geriatric Anesthesia Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, and colleagues from Department of Anesthesia, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China, investigated the effects of glucose on isoflurane-induced caspase-3 activation in H4 human neuroglioma cells. Their results are discussed in the article titled “Glucose May Attenuate Isoflurane-Induced Caspase-3 Activation in H4 Human Neuroglioma Cells,” published in this month’s issue of Anesthesia and Analgesia.
The investigators found that in cell culture 50 mmol/L (900 mg/100 mL) of glucose attenuated isoflurane-induced caspase-3 activity with a concomitant decrease in ROS and an improvement in ATP values. Glucose did not improve the decline in mitochondrial permeability following isoflurane. The researchers concluded that the beneficial effects of glucose are probably independent of mitochondrial function.
The authors note that a limitation of the study is the very high concentration of glucose and the outcomes are very preliminary. Nevertheless, this preliminary work will enable further studies using more clinically relevant concentrations of glucose. Perhaps hyperglycemia may be beneficial for the brain in specific clinical settings, which is an intriguing possibility.