Carbon monoxide and anesthesia-induced neurotoxicity

- Children commonly encounter anesthesia-related carbon monoxide (CO) exposure.
- CO is biologically active and can exert neurotoxicity or neuroprotection.
- Low dose CO limits anesthesia-induced neuronal apoptosis in newborn mice.
- Low dose CO modulates anesthesia-mediated oxidative stress in immature mouse brain.
- CO is an experimental therapy that may target 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.