Anesthesia-Induced Impairments of Developmental Synaptic Plasticity

When Nadia Lunardi, MD, PhD, applied for an IARS Mentored Research Award in 2014 as an Assistant Professor of Anesthesiology at the University of Virginia School of Medicine, she was not currently an American citizen and did not hold a green card. IARS was one of the few organizations at the time who offered opportunities to non-US native investigators to apply for funding. This chance opened for Dr. Lunardi when her 2014 application for the IMRA was accepted and allowed her to pursue her research on “Anesthesia-Induced Impairments of Developmental Synaptic Plasticity.” The goal of her IMRA-funded project was to establish how early exposure to anesthesia affected the trafficking and organization of synaptic vesicles in the developing brain, with special emphasis on the actin cytoskeleton. Through this investigation, Dr. Lunardi and her research team found that early-life anesthesia causes protracted disorganization of the highly regulated cycling of synaptic vesicles in developing synaptic hippocampal boutons. They also discovered that gene expression and protein levels of key regulators of pre-synaptic docking and fusion are altered in neonatal rats several days after exposure to anesthesia. This initial protected research time and the preliminary data collected through the study helped Dr. Lunardi successfully compete for an NIH K08 award and to progress in her career as a scientist. Today she serves as the Neuro Anesthesia Division Chief and Associate Professor of Anesthesiology at UVA and continues to develop the skills built during her IMRA-funded study. Her research has evolved towards two novel scientific areas: 1) the study of the role of sleep in anesthesia-induced cognitive dysfunction in the young and aging brain, and 2) the mechanisms underlying postoperative delirium. Below, Dr. Lunardi reflects on her journey as a researcher, her results and the implications from her IMRA-funded study and her hopes for the future of anesthesia research.

1. What is your current position?

Associate Professor of Anesthesiology, Neuro Anesthesia Division Chief 

2. How long have you been in this position?

Three years as Associate Professor, 6 months as Division Chief 

3. What was your role when you were first funded by IARS?

Assistant Professor of Anesthesiology

4. What was the goal of your initial research project?

The main goal of the project was to establish how early exposure to anesthesia affects the trafficking and organization of synaptic vesicles in the developing brain, with special emphasis on the actin cytoskeleton.  

5. Was it met?

Yes. We found that early-life anesthesia causes protracted disorganization of the highly regulated cycling of synaptic vesicles in developing synaptic hippocampal boutons. We also found that gene expression and protein levels of key regulators of pre-synaptic docking and fusion are altered in neonatal rats several days after exposure to anesthesia.

6. How did your findings impact patient care? How did your research impact the field of anesthesiology?

Although my findings did not translate directly into a patient’s care, they called attention to the idea that anesthetics are potent modulators of synaptic function and that they can impair neurons’ capacity to recover from changes in their homeostasis when administered during critical periods of vulnerability.  

7. Has your research subject area evolved since the award?

It very much has. The skills I learned during my IARS award were fundamental to evolve my research towards two novel scientific areas: 1) the study of the role of sleep in anesthesia-induced cognitive dysfunction in the young and aging brain, and 2) the mechanisms underlying postoperative delirium.  

8. How did the award affect your research/professional trajectory?

The award was instrumental in providing me with protected time for my research and to obtain the preliminary data necessary to successfully compete for an NIH K08 award. 

9. How do you feel about having received the IARS Mentored Research Award?

I feel privileged, incredibly grateful and lucky. At the time when I applied for the IARS Mentored Research Award, I was not an American citizen, nor did I hold a green card. The IARS was one of the very few organizations allowing non-US native investigators to apply for funding.

10. What would you like to convey to our donors, the people who made this award possible?

Thank you for donating to science and to the goal of raising the next generation of physician-scientists in Anesthesiology. Receiving a mentored research award from the IARS was life changing for me. 

11. What drew you to academic anesthesiology and to your particular area of research?

During my early years in Medical School, I was drawn to the most fundamental workings of the brain. I decided later on that I wanted to pursue a career that would allow me to directly apply this interest to patient care. 

12. What is something that someone would be surprised to learn about you?

I almost became a professional volleyball player before I decided to pursue Medical School.

13. What do you hope for the future of anesthesia research?

There is no denial that physician-scientists are struggling these days (in Anesthesiology, as well as in many other medical disciplines). Heavy clinical loads, a hospital leadership’s focus on financial rather than academic productivity, and an incredibly competitive funding environment are some of the contributing factors. My hope is for these challenges to reach the attention of leadership (Departmental Chairs, Anesthesiology societies and NIH leadership) so that change can be initiated.