Anesthesia, calcium homeostasis and Alzheimer's disease.
While anesthetics are indispensable clinical tools generally safe and effective, in some situations there is grown concern about selective neurotoxicity of these agents; the clinical significance is unclear as of yet. The mechanisms for inhalational anesthetics mediated cell damage are still not clear, although a role for calcium dysregulation has been suggested. For example, the inhaled anesthetic isoflurane decreases endoplasmic reticulum (ER) calcium concentration and increases that in the cytosol and mitochondria. Inhibition of ER calcium release, via either IP(3) or ryanodine receptors, significantly inhibited isoflurane neurotoxicity. Neurons made vulnerable to calcium dysregulation by overexpression of mutated presenilin-1 (PS1) or huntingtin (Q-111) proteins showed enhanced apoptosis upon isoflurane exposure. Sevoflurane and desflurane were less potent than isoflurane in altering intracellular calcium, and produced less apoptosis. Short exposures to inhalational anesthetics may provide neuroprotection by preconditioning via a sublethal stress, while prolonged exposures to inhalational anesthetics may induce cell damage by apoptosis through direct cytotoxic effects.
Wei
Huafeng
H
Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA. weih@uphs.upenn.edu
Xie
Zhongcong
Z
D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology
D018685:Anesthetics, Inhalation; D002118:Calcium