Research InterestsCerebrovascular surgery, Intracranial aneurysms and vascular malformations, Cerebral arterial bypass surgery, Carotid artery disease, Brain tumors, Neurooncology, Spinal vascular malformations, Spinal tumors
AcceptingFellows, Graduates, Summer Students
Keenan Endowed Chair in Surgery
St. Michael's Hospital
Scientist, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute
Professor of Surgery, University of Toronto
Keywords: Animal models, blood flow regulation, brain, human models, stroke, subarachnoid hemorrhage, vasoconstriction, vascular biology
Detailed Description: We study the causes and treatments for brain injury and damage after a variety of blood vessel disorders that affect humans. The work spans from basic laboratory work in animal models of these diseases to clinical trials and studies of humans with aneurysmal subarachnoid hemorrhage, brain hemorrhage and blood vessel malformations of the brain.
The goals of our laboratory are to define the cellular and molecular mechanisms that cause angiographic vasospasm, microvascular injury and poor outcome after subarachnoid hemorrhage, intracerebral hemorrhage (that can be a consequence of brain arteriovenous fistulas) and brain blood vessel fragility. The approach is translational and uses techniques ranging from animal surgery, molecular biology (PCR, Western blotting), immunohistochemistry to confocal imaging, microscopy and electrophysiology and focuses on mechanisms of brain injury after subarachnoid hemorrhage. The role of inflammatory cytokines such as tumor necrosis factor are also being studied in mouse models. We also study ion channels in vascular smooth muscle with and without vasospasm and how altering expression of ion channels to determine effects on vasospasm and vascular remodeling. We also use models of blood vessel malformations similar to arteriovenous fistulae in zebrafish in which we can then screen hundreds of drugs to figure out how to prevent the blood vessels from rupturing.
Second, we conduct extensive clinical work with patients where we are investigating mechanisms of poor outcome after subarachnoid hemorrhage, intracerebral hemorrhage and brain blood vessel malformations such as arteriovenous fistulas. Patients who survive these types of hemorrhages often have neurocognitive deficits. The etiology of these deficits is unknown and may involve processes other than vasospasm. We developed models in rats, mice and zebrafish, characterized neurobehavioral deficits in these animals and are examining mechanisms of dysfunction by electrophysiologic study of hippocampal function and molecular analysis of the brain.
Brain Slice, Endothelial Cells, Smooth Muscle cells
Procedures:Behavioral Tests, Electrophysiology, Gene Expression Analysis, Immunohistochemistry, In vitro electrophysiology, Isolated vessel preparation, Microarrays, qRT-PCR, RT-PCR, Stereotaxic brain surgery, Western Blot.
Amplifier, Analytical Balances, Benchtop Centrifuge, Blotting Apparatus, Culture Hood, Culture Incubators, Cryostat, Digidata, Dissecting Microscope, Electrophysiology rig, Fluorescence Microscope, Fresh Tissue sectioning systems, Gel Apparatus, Infusion apparatus, Low and Ultralow Freezers, Micropipette puller, Microwave Oven, Mini Vortexer, Real-Time/Thermocycler, Stimulator, Stirrer/Hot plate, Vibratome, Water baths
Within the Department of Physiology:
Outside the Department of Physiology
Philip Marsden Medicine, U of T, Canada
Andrew Baker Anesthesiology, U of T, Canada
Xiao-Yan Wen Research, U of T, Canada
About 50 other national and international collaborators in translational and clinical research
Committee member/officer of national/international scientific organizations
- 2014-2015 – International organizing committee, Vasospasm 2015 - 13th International Conference on Neurovascular Events after Subarachnoid Hemorrhage, September 17-19, 2015, Karuizawa Prince Hotel West, Karuizawa, Nagano, Japan
- 2015 – Co-chair, National Institutes of Health, National Library of Medicine subarachnoid hemorrhage common data elements project, February, 2015 – May, 2016
Publications and Awards
- Etminan N, Buchholz BA, Dreier R, Bruckner P, Torner JC, Steiger HJ, Hänggi D, Macdonald RL: Cerebral aneurysms: Formation, progression and developmental chronology. Translational Stroke Res 5:167-173, 2014
- Ladowski D, Qian W, Kapadia AN, Macdonald RL, Schweizer TA: Effect of aneurysmal subarachnoid hemorrhage on word generation. Behavioural Neurol 610868, 2014
- Kassardjian CD, Macdonald RL, Munoz DG: Hemangioblastomas in the elderly: epidemiology, clinical characteristics and pathology. J Clin Neurosci 21:1205-1208, 2014
- Ibrahim GM, Morgan BR, Macdonald RL: Patient phenotypes associated with outcomes following aneurysmal subarachnoid hemorrhage: a principal component analysis. Stroke 45:670-676, 2014
- Bell JD, Thomas TC, Lass EH, Ai J, Wan H, Lifshitz J, Baker AJ, Macdonald RL: Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage. J Neurosurg 121:1424-1431, 2014