Do Anesthetics Exacerbate Memory Deficits Following Traumatic Brain Injury?

At the age of 17, Sinziana Avramescu, MD, PhD, FRCPC, was involved in a car crash as a pedestrian and was sent unconscious to the ICU. While recovering from a traumatic brain injury, she became fascinated that all the tests said her brain was normal but she was not functioning at her previous capacity yet. This was the moment she decided to become a “brain scientist” to unravel this disconnect and help others experiencing traumatic brain injury. She did just that, dedicating her medical career to studying perioperative brain health. This passion and perseverance eventually led her to be recognized with the IARS Mentored Research Award in 2013 for her research, addressing the question, “Do Anesthetics Exacerbate Memory Deficits Following Traumatic Brain Injury?” A senior resident in the Department of Anesthesiology and Pain Medicine at the University of Toronto at the time, Dr. Avramescu’s overarching goal of this research program was to gain a better understanding of the debilitating consequences of traumatic brain injury (TBI) and to develop an informed pharmacological strategy to prevent post-traumatic memory deficits. The findings from this research provided the first proof-of-concept evidence that α5GABA_ARs are novel targets for pharmacologic treatment of persistent cognitive deficits induced by traumatic brain injury.

This motivated Dr. Avramescu and her mentor, Dr. Beverley Orser and collaborator and colleague, Dr. Stephen Choi, to co-found the Perioperative Brain Health Centre at Sunnybrook Health Sciences Centre, the first of its kind to focus on bringing together patients, healthcare professionals and researchers to design and implement novel diagnostic and treatment strategies for perioperative brain dysfunction.

In 2018, Dr. Avramescu moved to a community anesthesia practice at Humber River Hospital in Toronto, where she serves as the Executive Director in the Department of Anesthesia. She continues to be resolutely dedicated to furthering the knowledge around perioperative brain health, establishing the first perioperative research unit at Humber River Hospital. The unit and her hospital now partner with several academic centers across Canada, and serve as a research site for multi-center clinical trials. Below, Dr. Avramescu shares her research journey, her continued efforts to discover breakthroughs in the treatment of traumatic brain injury and how the IMRA helped her to be successful as a researcher, clinician and educator.

1. What was your role/title when you were first funded by IARS?

At the time of receiving my IARS Mentored Research Award, I was a senior resident in the Department of Anesthesiology and Pain Medicine at the University of Toronto.

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

I have been involved in research since my first year in medical school and research has been a constant passion throughout my career. Being a consumer of knowledge created by others was never enough for me, I always wanted to be involved in creating new knowledge and advancing the field of medicine. I knew that being part of a vibrant community of academic anesthesiologists at the University of Toronto would increase my chance of developing the skills and the tools I needed to contribute to my specialty.

Brain health, my particular area of research, has attracted me since I was 17 years old when I was a pedestrian involved in a car crash which sent me unconscious to the ICU. As I was recovering from this traumatic brain injury, I started thinking how fascinating it was that my brain was still not functioning at my previous capacity, although all the test results available at the time to assess the structure of my head were normal. That was the moment when I decided that one day, I will be a “brain scientist.” I still didn’t know at that time in what capacity, but I thought that using my brain to discover The Brain was the ultimate provocation and I decided to use my own experience with concussion as an inspiration to do more and help others.

3. What was the goal of your initial research project? Was it met?

The overarching goal of our research program was to gain a better understanding of the debilitating consequences of traumatic brain injury (TBI) and to develop an informed pharmacological strategy to prevent post-traumatic memory deficits. More specifically, we knew from our previous studies done in Dr. Oser’s laboratory that inflammation can upregulate a particular “memory blocking” receptor, the α5-subunit-containing GABA_A receptors (α5GABA_ARs) in the brain (Wang DS, Zurek AA, Lecker I, Yu J, Abramian AM, Avramescu S, Davies PA, Moss SJ, Lu WY, Orser BA). Memory deficits induced by inflammation are regulated by α5-subunit-containing GABA_A receptors (Cell Rep. 2012 Sep 27;2(3):488-96. doi: 10.1016/j.celrep.2012.08.022. Epub 2012 Sep 20. PMID: 22999935). Knowing that TBI causes brain inflammation, we postulated that TBI-induced memory deficits could be the result of an increased function of the α5GABA_ARs. And indeed, we were able to show that inhibiting these particular “memory blocking” receptors improved cognitive performance in mice (Khodaei S, Avramescu S, Wang DS, Sheng H, Chan NK, Lecker I, Fernandez-Escobar A, Lei G, Dewar MB, Whissell PD, Baker AJ, Orser BA). Inhibiting α5 subunit-containing γ-aminobutyric acid type A receptors attenuates cognitive deficits after traumatic brain injury (Crit Care Med. 2020 Apr; 48(4):533-544. doi: 10.1097/CCM.0000000000004161. PMID: 32205600).

4. How did your findings impact patient care?

Our findings are very important because they provided the first proof-of-concept evidence that α5GABA_ARs are novel targets for pharmacologic treatment of persistent cognitive deficits induced by traumatic brain injury. Moreover, these receptors can be detected using nuclear tags and MRI imaging and could serve in the future as an objective method to quantify memory loss associated with brain trauma.

5. How did your research impact the field of anesthesiology?

Brain health research is now a very important topic. With our population expected to live longer, we must do everything we can to preserve our brain health. And so, the angle of our research focus changed from a narrow lens on concussion, to a very broad area, perioperative brain health, because that is where we have the biggest impact as anesthesiologists. We also realized very early on that a successful perioperative research program required a multidisciplinary approach. In 2017, together with my mentor, Dr. Beverley Orser, and with my collaborator and colleague, Dr. Stephen Choi, we co-founded the Perioperative Brain Health Centre at Sunnybrook Health Sciences Centre. This is the first center of its kind that focuses on bringing together patients, healthcare professionals and researchers to design and implement novel diagnostic and treatment strategies for perioperative brain dysfunction, such as delirium, post-operative memory and executive function impairment. Additionally, I have extended my participation past the hospital walls, partaking in community outreach programs aimed at increasing medical literacy among patients and establishing patient-centered educational opportunities.

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

I was deeply honored to receive the IARS Mentored Research Award. This recognition was very important to me because it acknowledged my mentor, Dr. Beverley Orser, who had a massive impact on my research trajectory. My work would have been impossible without Dr. Orser’s mentorship and the support of our research team who helped me to succeed. The award belonged just as much to my fantastic colleagues in the Department of Anesthesia at Sunnybrook Health Sciences Centre who created a nurturing environment for me to succeed as a researcher, but also as a clinician and an educator. They were my work family, and I will remain forever grateful for their support and for their friendship.

7. Did the award affect your research/professional trajectory?

This award absolutely affected my professional trajectory, it offered me reassurance that my research was on the right track and the much-needed financial support to start my own research program. The award gave me the greatest privilege – protected time to focus on my research, to plan experiments and build relationships with other research teams. I felt incredibly lucky to be able to build a research career at the same time as being a clinician and an educator, which would have been impossible without this award.

8. What is your current position? How long have you been in this position?

In 2018, I moved to a community anesthesia practice and now I am an anesthesiologist at Humber River Hospital in Toronto, I serve as the Executive Director in the Department of Anesthesia, and I am the Secretary of the Medical Staff Association in our hospital.

9. What prompted you to leave academic medicine? In your current role, are you still involved in research? If so, in what ways? If not, how do you utilize the skills developed during your research path in this new role?

I continue to be heavily involved in research in my current position. In fact, I was able to create our first perioperative research unit at Humber River Hospital and now we partner with several academic centers across Canada, and we serve as a research site for multi-center clinical trials. I am also a member of our hospital’s Research Executive Committee, which establishes the research priorities and the vision for our Research Institute. I am directly involved with quality improvement initiatives and innovations through my participation as an active member of the Medical Quality Improvement Committee and of the Surgical Quality and Research Committee. I help organize innovative programs in our hospital, such as the “Physicians as Intensive Care Unit (ICU) Care Providers” program which was created during the COVID-19 pandemic to help our ICU nurse, and for which I was recognized with a College of Physicians and Surgeons of Ontario Council Award.

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

Many know that I am deeply passionate about research and education in general. Probably few know that I am also very passionate about spreading high level postgraduate education around the globe and representing our specialty worldwide. An international medical graduate myself, I became interested in international development, aid and collaboration since my early days in medical school. Now I am a board member of the Royal College Canada International, a non-profit, independent subsidiary of the Royal College of Physicians and Surgeons of Canada which conducts international outreach by forming academic collaborations with like-minded medical organizations around the world.