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2013 IARS Mentored Research Award $150,000

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Sinziana Avramescu, MD, PhD, FRCPC
University of Toronto
Toronto, Ontario, Canada


Dr. Avramescu's Research

Do anesthetics exacerbate memory deficits following traumatic brain injury?

Each year, approximately 1.7 million North Americans suffer a traumatic brain injury (TBI). Memory loss is one of the most common, persistent and devastating symptoms after TBI. Many TBI patients undergo procedures under general anesthesia which may exacerbate their memory deficits. No treatments are available to reduce these memory deficits, in part because an understanding of the underlying molecular mechanisms is lacking. Dr. Avramescu and her team previously identified a "memory blocking" receptor in the brain that is highly sensitive to anesthetics and is upregulated by inflammation. Since TBI initiates a strong inflammatory response in the brain, this "memory blocking" receptor may contribute to memory loss after TBI. Moreover, inflammation and anesthetics may act synergistically on this receptor and therefore anesthetics may further exacerbate memory deficits following TBI. Finally, inhibition of these "memory blocking" receptors has been shown to prevent long term memory deficits following anesthesia and inflammation. Their goal is to determine whether inhibiting this receptor reverses memory deficits after TBI and/or prevents anesthesia-induced exacerbation of memory loss. They plan to use an array of behavioral, biochemical and electrophysiological methods in a widely used rat model which effectively mimics TBI in humans.

With the proposed studies Dr. Avramescu's team will gain a better understanding of the debilitating consequences of TBI and will be able to develop an informed pharmacological strategy to prevent post-traumatic memory deficits. The results could rapidly lead to changes in clinical practice through the restricted use of drugs that enhance the activity of these "memory blocking" receptors or treatment with drugs that block their activity. Moreover, these receptors can be detected using nuclear tags and MRI imaging and could serve as the first method to quantify memory loss associated with general anesthetics and brain trauma.

 

Related publications

Memory deficits induced by inflammation are regulated by α5-subunit-containing GABAA receptors.

Wang DS, Zurek AA, Lecker I, Yu J, Abramian AM, Avramescu S, Davies PA, Moss SJ, Lu WY, Orser BA.

Systemic inflammation causes learning and memory deficits through mechanisms that remain poorly understood. Here, the authors studied the pathogenesis of memory loss associated with inflammation and found that we could reverse memory deficits by pharmacologically inhibiting α5-subunit-containing γ-aminobutyric acid type A (α5GABA(A)) receptors...

 
Read Dr. Avramescu's recent publications and articles.

Honors and Awards

Dr. Avramescu won the 2014 Junior Faculty Research Award at the 61st Annual Meeting of the Association of University Anesthesiologists for her project Inflammation Increases Brain Sensitivity to General Anesthetics.

 

At the International Anesthesia Research Society's 2014 Annual Meeting in Montreal, Canada, Dr. Avramescu won three different awards:

1) The Best of the Meeting Abstract Award for Basic Science

 

2) The Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Award for Best Abstract of Neuroscience in Anesthesiology and Perioperative Medicine

 

3) The Best in the Category Award: Best of Neuroscience in Anesthesiology and Perioperative Medicine for her presentation, "Inflammation Increases Neuronal Sensitivity To General Anesthetics In Mice"
Dr. Avramescu won the 2014 Junior Faculty Research Award at the 61st Annual Meeting of the Association of University Anesthesiologists for her project Inflammation Increases Brain Sensitivity to General Anesthetics.

 

Her work explains, in part, why critically ill patients frequently require lower doses of anesthetics compared with healthier patients and why anesthetic overdoses occur more frequently in critically ill patients. More information can be found on the University of Toronto's website.

 

As an anesthesia resident at University of Toronto, Dr. Avramescu presented at the 2012 Hospital for Sick Children Annual Perioperative Services Research Presentation & Competition. The judges selected Dr. Avramescu's presentation entitled "Inflammation increases neuronal sensitivity to anaesthetics" as the Best Laboratory Science Research Presentation. Dr. Avramescu spent six months in the Department of Physiology and returned as a research fellow to the Orser Lab in September 2012.