Roles Of Anesthetics In The Developing Brain
Neonatal exposure to anesthetics is associated with social interaction and cognitive deficits later on in life (Lin et al. 2016). To understand the underlying mechanisms that result in long-term functional change, we are investigating the roles of microRNAs, neuronal circuitry and morphology during development. Our goal is to move toward therapeutic interventions to attenuate the risks associated with anesthetics given to young children.
Two Roles Of Ketamine: Anesthetic And Antidepressant
Ketamine is commonly used as an induction agent for unconsciousness in children and adults. However in recent years, ketamine has been discovered as a novel treatment drug for depression. Will early-life exposure to ketamine result in depressive-like behavior later on in life? This is a paradoxical effect that has been shown with traditional antidepressant drugs that are selective serotonin reuptake inhibitors (SSRIs), when applied during early brain development. Our lab has initiated behavioral paradigms, cellular, molecular and electrophysiological approaches to investigate the effects of ketamine on the developing brain and the mechanism of its efficacy as an antidepressant.
Anesthetics As A Preconditioning Agent For Cerebral Ischemia
We are also examining the protective effects of anesthetic preconditioning against hypoxic and ischemic brain damage in adult rats. Cerebral ischemia is a frequent consequence during cardiac and neurological surgery. In surgical procedures with a high risk of ischemia, it is important to choose an anesthetic that offers protection. A focus of our studies is to examine how anesthetics work on the cellular and molecular level to enhance recovery after an ischemic insult. We found that the volatile anesthetic sevoflurane improves recovery after hypoxia by activating the mTOR pathway and increasing the expression of protein kinase Mζ. Additionally, we found that the local anesthetic and antiarrhythmic agent lidocaine reduces neuronal damage after hypoxia, an effect that is associated with reduced neuronal cell loss in the CA1 region of the hippocampus and improved learning and memory 4 weeks after ischemia.
Postnatal day 7 (P7) sevoflurane treated mice showed significant impaired social interactions in adulthood as shown by reciprocal social interaction (Figure 1) and three chamber social interaction (Figure 2) when compared to the no sevo treated mice. While the no-sevo treated group spent significantly more time exploring the novel object, the P7 sevo treated group did not show an increased interest when examined during adult (Figure 3).
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Wang, J., Meng, F., Cottrell, J. E., Sacktor, T. C., and Kass, I. S. (2012). Metabotropic actions of the volatile anaesthetic sevoflurane increase protein kinase M synthesis and induce immediate preconditioning protection of rat hippocampal slices. J. Physiol. 590, 4093-4107.
Esenther, B. R., Ge, Z., Meng, F., Cottrell, J. E., and Kass, I. S. (2013). Sevoflurane preconditioning attenuates the fall in adenosine triphosphate levels, but does not alter the changes in sodium and potassium levels during hypoxia in rat hippocampal slices. Anesthesiology 119, 119-128.
Lin, D., Liu, J., Kramberg, L., Ruggiero, A., Cottrell, J., and Kass, I. S. (2016). Early-life single-episode sevoflurane exposure impairs social behavior and cognition later in life. Brain Behav. 6, e00514.
Peng, Y., Zhang, W., Zhou, X., Ji, Y., Kass, I. S., and Han, R. (2016). Lidocaine did not reduce neuropsychological-cognitive decline in patients 6 months after supratentorial tumor surgery: a randomized, controlled trial. J. Neurosurg. Anesthesiol. 28, 6-13.
Peng, Y., Zhang, W., Kass, I. S., and Han, R. (2016). Lidocaine reduces acute postoperative pain after supratentorial tumor surgery in the PACU: a secondary finding from a randomized, controlled trial. J. Neurosurg. Anesthesiol. 28, 309-315.
Daisy Lin, Ph.D., Research Assistant Professor
Baiping Lei, M.D., Ph.D., Clinical Assistant Professor
Jinyang Liu, M.S., Research Scientist
Editorial Board: Journal of Neurosurgical Anesthesiology, Raven Press.
Member: Sub-Committee on Current Research, New York State Society of Anesthesiologists.