Richard J. Levy, MD

Our lab is interested in evaluating the neurotoxic and neuroprotective effects of low dose carbon monoxide (CO) in the developing brain. We are specifically focused on CO-mediated neuroprotection in the context of an anesthetic exposure. The phenomenon of re-breathing one’s own exhaled CO is unique to the semi-closed anesthesia breathing circuit. In early work, we found that exposure to low concentration CO alone inhibited natural programmed cell death in the developing murine brain and prevented necessary elimination of excess and aberrant neurons. This resulted in impaired social behavior and memory and learning later in life. In subsequent work, we found that the anti-apoptotic effects of CO were able to offset and prevent the deleterious effects of anesthetic agents in the developing brain. As a result, we are currently evaluating the mechanisms of anesthesia-induced overactivation of cytochrome oxidase within forebrain mitochondria in immature rodents and determining how CO modulates cytochrome oxidase activity during anesthetic exposure to provide neuroprotection. The ultimate goal of our work is to develop low dose CO as a novel therapeutic agent to prevent anesthesia-induced neurotoxicity.

In other work, we are studying fragile X syndrome, the leading known inherited intellectual disability and the most common genetic cause of autism. We are utilizing Fmr1 KO mice as a model of fragile X syndrome, intellectual disability, and autistic behavior. In preliminary work, we found a defect in the mitochondrial pathway of apoptosis in the forebrain of newborn male Fmr1 mutant mice. This led us to explore oxidative phosphorylation and bioenergetic capacity in these mice. We are currently studying mitochondrial function in the developing brain of Fmr1 KOs and determining the genetic predisposition to oxidative stress and neurodegeneration. We aim to use this model to identify neurotoxic and neurosparing anesthetic agents for FXS and related diseases. The ultimate goal of this work is to develop safe and precise anesthetic approaches for children with FXS.