In the SUNY Downstate Anesthesiology Neuroscience Laboratory, we study the mechanisms by which anesthetics alter neuronal metabolism, intracellular signaling, synaptic activity, behavior, learning and memory.
Specifically, we study the deleterious actions of volatile anesthetics when neonatal mice are subjected to anesthesia and examine the mechanisms by which these agents lead to altered adolescent and adult behavior. We measure the electrophysiological, cellular and molecular changes that correlate with long-term behavioral changes. In addition, we examine the electrophysiological and biochemical mechanisms by which anesthetics improve recovery after hypoxia and ischemia in adult rats.
Anesthesia during perinatal brain development has been implicated as leading to learning and memory deficits in later life. We are using mice to investigate the mechanisms by which anesthetics in the neonatal period may cause social, behavioral, learning and memory changes in adolescent and adult mice. Preliminary results have found alterations in social behavior and we are examining the physiological, cellular and molecular actions of anesthetics in order to determine the mechanisms by which they cause toxicity.
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 the effects of anesthetics and other agents to determine how the cellular and molecular changes due to these anesthetics enhance recovery after an ischemic insult. We found that the volatile anesthetic sevoflurane improves recovery after hypoxia in hippocampal slices and after global ischemia in situ. Sevoflurane activates the mTOR pathway increasing the expression of protein kinase Mζ; blocking this pathway prevents the protective effects of sevoflurane. Additionally, we found that the local anesthetic and antiarrhythmic agent lidocaine reduces neuronal damage after hypoxia in hippocampal slices and after global or focal ischemia in situ. After global ischemia we found that lidocaine not only reduced neuronal cell loss in the CA1 region of the hippocampus but improved learning and memory 4 weeks after ischemia.
Lastly, in seeking to improve the estimation of anesthesia depth, we wish to compare changes in human electrocardiogram (EKG) and electroencephalogram (EEG) under general anesthesia, to depth of anesthesia as scored by BIS monitor. We plan to apply a novel mathematical method of analysis to identify if the changes in the BIS score correlate with a detectable pattern and/or rate change in the EKG. If successful, these EKG patterns during anesthesia could provide an independent measure to estimate the depth of anesthesia, in addition to the BIS monitor.
Ira S. Kass, PhD, Professor of Anesthesiology, Professor of Physiology and Pharmacology
Hai Lin, PhD, Research Scientist
Jinyang Liu, MS, Research Scientist
Protein Kinase Mζ is a brain-specific protein essential for the formation and maintenance of long-term memory. Moreover, it has a protective role against hypoxia and ischemia in the neuron. Sevoflurane, a widely used inhaled anesthetic has shown to be associated with an increase in new PKMζ protein in the hippocampus of the brain (Wang et al., J Physiol. 590:4093, 2012). To study the mechanisms that control the synthesis of PKMζ, we study if the pools of protein synthesized during sevoflurane application and long-term memory maintenance, may break down in some pathological conditions or during emergence from anesthesia in mice and rats.
Additionally, to study the possible involvement of PKMζ in mediating the neuroprotective effects of other anesthetics, we are also currently examining whether a brief application of dexmedetomidine has similar effects to those of sevoflurane. Our basic science research results may be important toward understanding memory loss and post-operative cognitive dysfunction experienced by a subset of patients exposed to anesthetics.
James E. Cottrell, MD
Todd C. Sacktor, MD
Panayiotis Tsokas, PhD
Cardiovascular Research Lab
The Cardiovascular Research Lab in the Anesthesia Dept. of SUNY Downstate is devoted to basic science research of ischemia/reperfusion (I/R) injury. We collaborate with scientists and clinicians to translate our findings into clinical study of I/R injury. Besides animal models of I/R injury, we team up with anesthesiologists, cardiac surgeons, cardiologists, and the transplantation team to develop multiple clinical research projects on cardiovascular diseases and transplantation rejection. The project is funded by NIH.
The second major research area of my lab is to investigate the cause of preeclampsia, a pregnancy disease with high prevalence among African American women whom SUNY Downstate serves. My lab has teamed up with physicians at Anesthesia and Obstetric departments to study the profile of inflammation in these patients. The project has been funded by New York State and the SUNY Downstate President Award. Our recent findings were published in Journal of Reproductive Immunology, 2015 Jan 3. pii: S0165-0378(14)00161-2. doi: 10.1016
Ming Zhang, MD, PhD
Dept. of Anesthesiology and Dept. of Cell Biology