Our Work — CEREBRI

Improving outcomes for patients suffering an ischemic brain injury

CEREBRI, the Collaborative Entity for REsearching BRain Ischemia, is a University of British Columbia (UBC) funded research cluster. CEREBRI comprises a multidisciplinary team of scientists, health care providers, healthy policy makers, and patient partners to advance our knowledge on ischemic brain injury. As a translational research cluster, our aims span from basic sciences where we aim to elucidate the fundamental disease mechanisms of ischemic brain injury through to survivorship and improving long-term patient outcomes. A central mandate of CEREBRI is to integrate research into clinical care, through which, four research pillars have arisen:

OUR RESEARCH PILLARS

Pillar 1: Diagnosis

Alternative diagnostic tools with greater accuracy and generalizability are required, particularly in rural communities where resources are sparse. Therefore, this research theme will focus on validating improved diagnostic tests that are logistically feasible to implement province and nation wide.

Pillar 2: Pathophysiology

A hurdle to improving our understanding of the disease mechanisms of ischemic brain injury is the difficulties associated with acquiring human brain tissue samples. Access to clinical biospecimens from patients that have experienced an ischemic brain would enable collaboration between the clinical and basic neurosciences and facilitate discovery-based analyses to improve out understanding of ischemic brain injury disease mechanisms. Therefore, this research theme will focus on the creation of a biobank of human tissue biospecimens including blood, cerebrospinal fluid, and brain tissue from patients that have experienced an ischemic brain injury to enable basic neuroscience and translational research into ischemic brain injury pathophysiology.

Pillar 3: Patient Management

The past two decades have seen a nominal improvement in the outcome of patients that experience and ischemic brain injury. This is attributable to a lack of effective therapies as well as treatment strategies that can be employed province and nation wide, including in rural and remote jurisdictions. Therefore, this research theme will focus on investigating the biologic, physiologic and clinical efficacy of medical interventions for treating ischemic brain injury that can be applied in all provincial and national healthcare settings.

Pillar 4: Patient Outcomes

Clinical outcome assessments of ischemic brain injury focus on rudimentary dichotomous scales that are not patient centered and do not capture the intricacies of neurologic function in survivors of an ischemic brain injury. This research theme will focus on evaluating detailed neurocognitive outcome assessments that capture important cognitive, psychiatric, and patient focused aspects of recovery from ischemic brain injury in a more holistic manner. An emphasis will be placed on validating outcome assessments that can be conducted virtually to mitigate participant attrition and improve accessibility for patients in rural communities.

Ongoing CEREBRI Projects

DIFFUSION - Canadian Institutes of Health Research (CIHR)

This research project aims to prospectively differentiate between pathophysiologic phenotypes of hypoxic ischemic brain injury (HIBI), delineate the underlying mechanisms and determine the associated clinical outcomes.

PI: M. SEKHON

INFLAME - Heart and Stroke Foundation of Canada

Hypoxic ischemic brain injury (HIBI) remains a devastating clinical entity and is need of advances to identify promising therapeutic options. Our study will unravel important insights into ischemic brain disease in vivo in humans. Our experimental design utilizes longitudinal measures to characterize the dynamic nature of an immuno-pathologic response in HIBI, integrates in situ highly granular physiologic neuromonitoring to provide cerebrovascular context and encompasses analyzing cerebral arterio-venous differences of analytes to isolate brain physiology in an otherwise, multi-system disease (post-cardiac arrest syndrome). Identification of specific immunomodulatory pathways holds promise to identify promising therapeutics that can be widely administered in any BC healthcare setting (e.g. immunomodulatory medications such as IL-1β receptor blockade). This goal is contrasted with the current management approaches (targeted temperature management and related extra-corporeal specialized organ support devices) for HIBI, which can only be conducted in highly specialized tertiary care hospitals. It is imperative that therapeutics that can be widely distributed at all BC healthcare settings (especially rural and underserved communities) be sought.

PI: M. SEKHON & R. HOILAND

EVALUATE - The Canadian Donation and Transplantation Research Program (CDTRP)

The goal of this project is to characterize the cerebrovascular physiology of circulatory death during withdrawal of life sustaining therapies in humans.

PI: M. SEKHON

EVALUATE MAID - VGH & UBC Hospital Foundation

The goal of this project is to characterize the cerebrovascular physiology of circulatory death in patients undergoing medical assistance in dying (MAID).

PI: M. SEKHON

NONOFLOW - VGH & UBC Hospital Foundation

A central goal of this study is to demonstrate the absence of cerebral blood flow and function following abdominal normothermic regional perfusion (A-NRP), thereby improving clinical confidence regarding its safety and maintenance of adherence to death determination in organ donors.

PI: M. SEKHON

INFORM - Heart and Stroke Foundation of Canada

The major aim of this research proposal is to test the hypothesis of whether the changes in PaCO2 observed upon initiation of Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO) results in increased biomarkers of neurologic injury, and if this injury is mediated by reduction in cerebral blood flow to a level that results in cerebral ischemia, and characterize clinical and radiographic neurologic injury in this population.

PI: D. GRIESDALE & S. THIARA

TRANSFUSION - Canadian Institutes of Health Research (CIHR)

This study investigates the biologic effects and mechanisms underpinning augmenting arterial oxygen content by red blood cell transfusion on mitigating secondary injury in patients with hypoxic ischemic brain injury disease following resuscitation from cardiac arrest, and the impact of nitrosylated hemoglobin physiology following red blood cell transfusion and its impact cerebral blood flow, oxygen delivery and metabolism.

PI: M. SEKHON & R. HOILAND

Intimate Partner Grant - US Department of Defense

PI: C. WELLINGTON