Carbon monoxide and anesthesia-induced neurotoxicity.
The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve activation of the oxidative stress-associated mitochondrial apoptosis pathway. Targeting this pathway could result in prevention of anesthetic toxicity in the immature brain. Carbon monoxide (CO) is a gas that exerts biological activity in the developing brain and low dose exposures have the potential to provide neuroprotection. In recent work, low concentration CO exposures limited isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice and modulated oxidative stress within forebrain mitochondria. Because infants and children are routinely exposed to low levels of CO during low-flow general endotracheal anesthesia, such anti-oxidant and pro-survival cellular effects are clinically relevant. Here we provide an overview of anesthesia-related CO exposure, discuss the biological activity of low concentration CO, detail the effects of CO in the brain during development, and provide evidence for CO-mediated inhibition of anesthesia-induced neurotoxicity.
Department of Anesthesiology, Columbia University Medical Center, United States. Electronic address: rl2740@cumc.columbia.edu.
Richard J
RJ
Levy
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002248:Carbon Monoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007530:Isoflurane / Q000009:adverse effects*; D008928:Mitochondria / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology
D002248:Carbon Monoxide; D007530:Isoflurane
Anesthesia-induced neurotoxicity; Apoptosis; Carbon monoxide; Cytoprotection; Endogenous; Exogenous; Exposure; General anesthesia; Low-flow anesthesia; Mitochondria; Oxidative stress; Therapy