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R. David Andrew PhD
 R. David Andrew
Position(s)
Professor
Contact Info

Faculty Bio

My lab is currently studying how our higher brain is incredibly susceptible to global ischemia (as during sudden heart failure), while our brainstem is dramatically resistant. This is best demonstrated by the tragic development of the `persistent vegetative state` where a brain-injured patient is awake but not aware...because only their lower brain is functioning. Studying how the lower brain resists damage should reveal clues as to why our higher brain is so susceptible to injury.

In related studies, we have been exploring the origin of spreading depolarizations (SD) in the brains of mammals and insects.
This mass loss of membrane potential spreads across gray matter, quieting the brain during trauma or stroke, but also quickly leading to neuronal death. The electrical and molecular details of this mechanism have remained a mystery, but we are gaining insight not previously considered by researchers. Unravelling this story will provide considerable insight as to how to protect neurons from loss of blood flow during cardiac arrest, stroke and head trauma.

Curriculum Vitae (recent)

June 2021
 

NAME                                                  Robert  David  ANDREW 

CITIZENSHIP                                      Canadian 

POSITIONS HELD                              Assistant Professor, appointed 1982

                                                               MRC Scholarship, July 1983 - June 1988

                                                             Associate Professor, appointed 1988

                                                               Tenure awarded, 1988

                                                             Professor, appointed 1993

 

CONTACTS                                       Department of Biomedical and Molecular Sciences

                                                           and the Centre for Neuroscience Studies

                                                           Queen's University, Kingston, Ontario  K7L 3N6.

                                                           Cell: (613) 453-1380

                                                           Office: (613) 533-2860                         

                                                           Email: andrewd@queensu.ca or andrewd.queensu@gmail.com                                                                        

UNIVERSITY EDUCATION               B.Sc. (Hon.), University of Western Ontario, Dept. Zoology

                                                                                                London, Canada, 1973.

                                                           M.Sc., University of Western Ontario, Dept. Zoology

                                                                                                London, Canada, 1975.

                                                           Ph.D., Dept. Biology, York University,

                                                                                                Toronto, Canada, 1979.

 

POSTDOCTORAL                               Postdoctoral Fellow, Dept. Zoology,

                                                                                University of Toronto, Toronto, July 1979 - June 1980.

 

                                                             Postdoctoral Fellow, Dept. Physiology,

                                                                                Tulane Medical School, New Orleans, July 1980 - August 1982.

                                                                                MRC Postdoctoral FellowshipJuly 1980 - June 1982

 

CURRENT RESEARCH SUPPORT

New Frontiers in Research Fund – Exploration Award. `The early molecular events setting up acute brain injury`. Funded April 2021 to March 2023.  $100K  per year + $25K indirect costs.

NSERC Operating Grant. ‘Converting the Na/K pump into a shutdown channel’. Funded 2017-2023, $26K  per year. 

Heart and Stroke Foundation of Canada Operating Grant.  ”Activation and opening of the channel that kills neurons during ischemia  Funded July 2019-June 2021  $96K per year. Extended to June 2022.

Graduate Supervision

Currently supervising one post-doc, two doctoral students, two MSc students and two summer project students.

Graduated a total of 9 doctoral students and 32 MSc students.

Supervised 32 fourth-year project students.

TEACHING

ANAT 312/812*                   Functional Neuroanatomy

NSCI 429/829*                    Disorders of the Nervous System - Course Coordinator

NSCI 499                             Research Projects in Neuroscience

NSCI 444/844*                    Controversies in Neuroscience - Course Coordinator

PEER-REVIEWED PUBLICATIONS (past 10 years)

Andrew RD, Hartings JA, Ayata C, Brennan KC, Dawson-Scully KD, Farkas E, Herreras O, Kirov SA, Müller M, Ollen-Bittle N, Reiffurth C, Revah O, Robertson RM, Shuttleworth CW, Ullah G, Dreier JP. (in press). Spreading depolarization: consensus, contention, and questioning the role of glutamate excitotoxicity in brain damage. Neurocritical Care.

Hellas J and Andrew RD. (in press) Neuronal swelling: A non-osmotic consequence of spreading depolarization. Neurocritical Care.

Mehder RH, Bennett BM, Andrew RD. (2021) Age-related neuronal deterioration specifically within the dorsal hippocampus in a mouse model of late onset Alzheimer's disease. J Alzheimer`s Disease.79: 1547–1561.

DOI 10.3233/JAD-201024

Ghoweria AO, Gagolewicz P, Fraziera HE, Ganta JC, Andrew RD, Bennett BM, Thibault O. (2020) Neuronal calcium imaging, excitability, and plasticity changes in the Aldh2–/– mouse model of sporadic Alzheimer’s disease. J Alzheimer`s Disease 77:1623–1637. DOI 10.3233/JAD-200617

Lowry CA, Golod ME, Andrew RD, Bennett BM (2020) Expression of neuronal Na+/K+-ATPase a subunit isoforms in the mouse brain following genetically programmed or behaviorally induced oxidative stress. Neuroscience 442: 202-215.

Shuttleworth CW, Andrew RD, Akbari Y, Ayata C, Brennan KC, et al. (2020). Which spreading depolarizations are deleterious to brain tissue? Neurocritical Care 32 (1), 317-322.doi: 10.1007/s12028-019-00776-7.PMID: 31388871

Mehder RH, Bennett BM, Andrew RD. (2020) Morphometric analysis of hippocampal and neocortical pyramidal neurons in a mouse model of late onset Alzheimer's disease. J Alzheimer`s Dis. doi: 10.3233/JAD-191067.

Robertson RM, Dawson-Scully KD, Andrew RD. (2020) Neural shutdown under stress: an evolutionary perspective on spreading depolarization. J Neurophysiol. 123(3):885-895. doi: 10.1152/jn.00724.2019. Epub 2020 Feb 5 PMID: 32023142

Petrin D, Gagolewicz PJ, Mehder RH, Bennett BM, Jin AY, Andrew RD. (2019). Spreading depolarization and neuronal damage or survival in mouse neocortical brain slices immediately and 12 hours following middle cerebral artery occlusion. J Neurophysiol.121(5): 1650-1663. PMID: 30811255

Ventura, NM, Li TY Tse, MY, Richard L, Tayade C, Jin AY, Andrew RD, Pang SC. (2018). Developmental origins of pregnancy-induced cardiac changes: Establishment of a novel model using the atrial natriuretic peptide gene-disrupted mice. Mol Cell Biochem. 2018 Dec;449(1-2):227-236. doi: 10.1007/s11010-018-3359-z. 

Andrew RD, Hsieh YT, Brisson CD. (2017) Spreading depolarization triggered by elevated potassium is weak or absent in the rodent lower brain., 7-2016 (e-pub), J Cereb Blood Flow Metab. 2017 May;37(5):1735-1747. doi: 10.1177/0271678X16657344.

Hartings JA, Shuttleworth CW, Kirov SA, Ayata C, Hinzman JM, Foreman B, Andrew RD et al., (2017) The continuum of spreading depolarizations in acute cortical lesion development: Examining Leao's legacy., J Cereb Blood Flow Metab. 2017 May;37(5):1571-1594. doi: 10.1177/0271678X16654495.

Dreier JP, Fabricius M, Ayata C, ...Andrew RD et al. (2017) Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group. J Cereb Blood Flow Metab. 2017 May;37(5):1595-1625. doi: 10.1177/0271678X16654496.

Spong KE, Andrew RD, Robertson RM, (2016) Mechanisms of spreading depolarization in vertebrate and insect central nervous systems., 10-2016, J. Neurophysiology, Vol. 116(3):1117-27.

Hubel N, Andrew RD, Ullah G, (2016) Large extracellular space leads to neuronal susceptibility to ischemic injury in a Na+/K+ pumps-dependent manner., 5-2016, J. Neurophysiology, Vol. 40(2):177-92

Andrew RD. (2015) The Persistent Vegetative State: Evidence That the Lower Brain Survives Because Its Neurons Intrinsically Resist Ischemia. M.M. Monti, W.G. Sannita (eds.), Brain Function and Responsiveness in Disorders of Consciousness, © Springer International Publishing Switzerland 2016 DOI 10.1007/978-3-319-21425-2_10

Ventura NM, Jin AY, Tse MY, Peterson NT, Andrew RD, Pang SC. (2015). Onset and Regression of Pregnancy-Induced Cardiovascular Alterations in Gestationally-Hypertensive Mice: The Role of the Natriuretic Peptide System. Biol. Reprod. Dec; 93(6):142. doi: 10.1095/biolreprod.115.132696.

Ventura NM, Jin AY, Tse MY, Peterson NT, Andrew RD, Mewburn JD, Pang SC. (2015). Maternal hypertension programs increased cerebral tissue damage following stroke in adult offspring. Molecular and Cellular Biochemistry 408(1): 223-233.

D'Souza Y, Elharram A, Soon-Shiong R, Andrew RD, Bennett BM. (2015). Characterization of Aldh2-/- mice as an age-related model of cognitive impairment and Alzheimer's Disease. Molecular Brain 8:27. doi: 10.1186/s13041-015-0117-y.

Brisson CD, Jin AY, Andrew RD. (2014) Brainstem neurons resist the same acute ischemia that injures higher neurons: Insight to the persistent vegetative state.  PLoS ONE. 9(5): e96585.  doi:10.1371/journal.pone.0096585

Ventura NM, Jin AY, Peterson NT, Tse MY, Andrew RD, Pang SC. (2014) Molecular adaptations in vasoactive systems during acute stroke in salt-induced hypertension.  Molecular and Cellular Biochemistry: 399(1-2):39-47.

Brisson CD, Lukewich MK, Andrew RD. (2013) A distinct boundary between the higher brain`s susceptibility to ischemia and the lower brain`s resistance. PLoS ONE. 8(11): e79589. doi:10.1371/journal.pone.0079589

Brisson CD, Andrew RD. (2012) A neuronal population that dramatically resists acute ischemic injury independent of blood supply. J Neurophysiol  108: 419-430.

White SH, Brisson CD, Andrew RD. (2012) Examining protection from anoxic depolarization by the drugs dibucaine and carbetapentane using whole-cell recording from CA1 neurons. J Neurophysiol 107:2083-2095.

Douglas HA, Callaway JK, Sword J, Kirov SA, Andrew RD. (2011) Potent inhibition of anoxic depolarization by the sodium channel blocker dibucaine. J Neurophysiol 105:1482-94.

Research Interests

My interest in Neuroscience developed while carrying out electron microscopical studies comprising my M.Sc. studies at the University of Western Ontario. Subsequently during Ph.D. research at York University in Toronto, I utilized electrical stimulation of nervous tissue to increase neurohormone release as studied ultrastructurally and biochemically. From that work I decided to learn more about neurophysiological techniques as research tools. As a post-doc at the Tulane Medical School with Dr. Ed Dudek, I studied the electrophysiology of mammalian neuroendocrine cells and used live hippocampal slices to examine electrotonic coupling among neurons.

This approach continued in my own lab, evolving into neurophysiological studies of neuronal swelling caused when neurons are osmotically challenged, become hyperactive (as during epilepsy) or are metabolically challenged (as during stroke). Recording intracellularly from neurons or astrocytes (or extracellularly from neuronal populations) can be combined with simultaneous imaging techniques. For example, imaging light transmittance through live brain slices is a dramatic way to monitor tissue swelling and injury. I have collaborated with Dr. Sergei Kirov using 2-photon scanning laser confocal microscopy that reveals volume changes and damage to single neurons and glial in real time. Individual brain cells can be imaged in transgenic rodents engineered so that a few cells are dramatically fluorescent on a dark background in the live state. We are particularly interested in how neurons and glia respond during the early period of simulated stroke or head trauma. We can then assess potentially therapeutic drugs that reduce or prevent acute neuronal injury.

One particular research interest is a phenomenon termed spreading depression (SD), a migrating depolarization of brain cells that can be imaged in neocortical and hippocampal brain slices. Spreading depression underlies the aura (e.g. flashing lights or numbness) preceding migraine headache and may actually be a cause of migraine pain, rather than just a symptom.  A related aspect is a process similar to spreading depression termed anoxic depolarization (AD). As soon as cortical tissue experiences severe metabolic stress (as during stroke or head trauma), AD generation contributes even more stress, damaging neurons wherever it propagates. AD-like events (peri-infarct depolarizations, PIDs) recur and expand brain damage in the hours following stroke or brain trauma. My Neurologist colleague Dr. Al Jin and I collaborate to investigate drugs that reduce such damage in brain slices by blocking the AD. They also inhibit SD. We consider AD and PID inhibition to be the key targets for improving patient outcome following stroke or traumatic brain injury.

Most recently we are carrying out single channel recordings in mammalian neurons undergoing ischemia to discover the fundamental molecular mechanisms underlying acute neuronal death that can quickly develop following spreading depolarization (SD) in the gray matter of the higher brain. By identifying the channel that opens to drive SD, we are now able to search for an SD `activator` released by the ischemic gray matter that evokes that opening to generate SD and the neuronal injury that follows in its wake.