Curriculum Vitae (recent)

C U R R I C U L U M   V I T A E  (short)
 
November, 2018

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.
                                                                                Tel: (613) 533-2860
                                                                                Fax:  (613) 533-2566                         
                                                                                Email: andrewd@queensu.ca
                                                                                Webpage: http://meds.queensu.ca/faculty/david_andrew
 
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 Fellowship, July 1980 - June 1982
 
SCIENTIFIC AFFILIATIONS
Heart and Stroke Foundation of Canada
Scientific Review Committee III, 2001-2004; 2007-2010
Funded by HSFC 1995 - 2012
Canadian Institutes of Health Research
Operating Grants Panel (Neuroscience A), 2010-11
Funded by MRC/CIHR 1983 - 2007
Ontario Ministry of Research and Innovation 
   - Early Researcher Award Panel, 2007
 Canadian Physiological Society
   - Councilor, 2002-2005 
Editorial Board, Experimental Neurology, 1989 – 2000                                               
Heart and Stroke Foundation of Ontario                                                                         
   -  Research and Development Review Committee, 1994 – 96
Medical Research Council of Canada
   -  Operating Grants Committee (Neurosciences), 1989-90
Canadian Association of Anatomists
   -  Science Policy Committee, 1989-90
Society for Neuroscience
International Brain Research Organization
Canadian Association for Neuroscience
Canadian Epilepsy Consortium (CEC), Associate Member
               
EXTRACURRICULAR
Triathlete for the past 25 years.
Skiing, hockey, snowboarding, cycling, windsurfing, sailing
 
 REVIEWED PUBLICATIONS (past 15 years)
 
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. Molecular and Cellular Biochemistry. Accepted: April 13, 2018.

Andrew RD, Hsieh YT, Brisson CD. (2016) Spreading depolarization triggered by elevated potassium is weak or absent in the rodent lower brain., 7-2016 (e-pub), J. Neurophysiology

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

Hartings JA, Shuttleworth CW, Kirov SA, Ayata C, Hinzman JM, Foreman B, Andrew RD, et al., (2016) The continuum of spreading depolarizations in acute cortical lesion development: Examining Leao's legacy., 7-2016 (e-pub), J Cereb Blood Flow Metab.

Dreier JP, Fabricius M, Ayata C, ...Andrew RD et al., (2016) Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group., 7-2016 (e-pub), J Cereb Blood Flow Metab.

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.
 
Risher WC, Andrew RD, Kirov SA. (2009). Real-time passive volume responses of astrocytes to acute osmotic and ischemic stress in cortical slices and in vivo revealed by two-photon microscopy. Glia  57:207-21.
 
Fraser DD, Andrew RD (2008). Perivascular aquaporins :  Potential post-ischemic therapeutic drug targets? Critical Care Medicine 36: 2701-2.
 
Scott CA, Rossiter JP, Andrew RD, Jackson AC (2008) Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome in experimental rabies in yellow fluorescent protein-expressing transgenic mice. J Virology  82:513-21.

Stroman PW, Lee AS, Pitchers KK, Andrew RD. (2008) Magnetic resonance imaging of neuronal and glial swelling as an indicator of function in cerebral tissue slices. Magn Reson Med. 59:700-6.

Davies ML, Kirov SA, Andrew RD. (2007) Whole isolated neocortical and hippocampal preparations and their use in imaging studies. J. Neurosci. Meth. 166 : 203-216.
 
Andrew RD, Labron MW, Boehnke SE, Carnduff L, Kirov SA. (2007) Physiological evidence that CNS neurons lack functional aquaporins. Cerebral Cortex 17 : 787-802    doi:10.1093/cercor/bhk032
 
Anderson, T. R., C.R. Jarvis, A.J. Biedermann and R. D. Andrew (2005) Blocking the anoxic depolarization: neuroprotection without functional compromise following simulated stroke in cortical brain slices. J. Neurophysiol. 93: 963 - 979.
 
Church A.J. and R.D. Andrew (2005) Spreading depression expands primary traumatic injury in the neocortical slice. J. Neurotrauma  22:  277-290.
 
Andrew, R. D., R. Hunt, J. Leroux, M. McAuley and S.C. Pang (2004) A Collection of Neuroanatomy Images. Queen`s University Press.
 
Wang, W., B. Murphy, K. E. Dow, R. D. Andrew and D. D. Fraser (2003) Systemic adrenocorticotropic hormone (ACTH) administration down-regulates the expression of corticotropin releasing hormone (CRH) and CRH-binding protein (CRH-BP) in infant rat hippocampus.  Pediatric Research 55, 604-610.
 
Fraser, D.D., S. Whiting, R.D. Andrew, A. MacDonald, K. Musa, S.C. Cunnane (2003) Elevated polyunsaturated fatty acids in blood serum obtained from children on the ketogenic diet.  Neurology 60, 1026-1029.
 
Anderson, T. R. and R. D. Andrew (2002) Spreading depression: Imaging and blockade in the rat neocortical slice.   J. Neurophysiol. 88,  2713-2725.
 
Andrew, R. D., A.J. Biedermann, T.R. Anderson and C.R. Jarvis (2002) Imaging and preventing spreading depression independent of cerebral blood flow.  In: Brain Activation and CBF Control.  Eds M. Tomita, I. Kanno and E. Hamel.  Elsevier Sciences.
 
Jarvis, C.R., T.R. Anderson and R.D. Andrew (2001) A spreading anoxic depolarization during O2/glucose deprivation mediates acute neocortical damage independent of glutamate.  Cerebral Cortex 11, 249-259.
 
Joshi, I. and R.D. Andrew (2001) Imaging anoxic depolarization during ischemia-like conditions in the mouse hemi-brain slice.  J. Neurophysiol. 85,  414-424.
 
Mendoza-Fernández, V., R.D. Andrew and C. Barajas-López (2000) ATP inhibits glutamate synaptic release by acting at P2Y receptors in pyramidal neurons of hippocampal slices.  J. Pharm. Exper. Therapeut. 293,  172-179.
 
Andrew, R. D., T.R. Anderson, A.J. Biedermann, I. Joshi and C.R. Jarvis (2000) Imaging the anoxic depolarization, a multifocal and propagating event. In: Pharmacology of Cerebral Ischemia 2000,  Eds. J. Krieglstein  and S Klumpp,  Medpharm Scientific Publishers, Stuttgart, pp. 75-94.
 
Obeidat, A.S., C.R. Jarvis and R.D. Andrew (2000)  Glutamate does not mediate acute neuronal damage induced by oxygen/glucose deprivation in the hippocampal slice.  J. Cereb. Blood Flow Metab. 20, 412-422.
 
Mendoza-Fernández, V., R.D. Andrew and C. Barajas-López (2000). Interferon inhibits long-term potentiation and unmasks a long-term depression in the rat hippocampus. Brain Research  885, 14-24.
 
Jarvis, C.R., L. Lilge, G. Vipond and R.D. Andrew (1999)  Interpretation of intrinsic optical signals and calcein fluorescence during excitotoxic insult in the hippocampal slice.  NeuroImage 10, 357-372.
 
Andrew, R.D., C.R. Jarvis and A.S. Obeidat (1999)  Potential sources of intrinsic optical signals imaged in live brain slices.  METHODS: A Companion to Methods in Enzymology  18, 185-196.
 
Basarsky, T.A., S. Duffy, R.D. Andrew, and B.A. MacVicar. (1998) Imaging spreading depression and associated calcium dynamics in brain slices.  J. Neurosci. 18, 7189-7199.
 
Obeidat, A.S. and R.D. Andrew (1998) Spreading depression determines acute neuronal damage in the hippocampal slice during oxygen/glucose deprivation.  Europ. J. Neurosci. 10, 3451-3461.
 
Polischuk, T.M., C.R. Jarvis and R.D. Andrew (1998) Intrinsic optical signaling denoting neuronal damage in response to acute excitotoxic insult by domoic acid in the hippocampal slice.  Neurobiol. Disease 4, 423-437
 
Andrew, R.D., M.E. Lobinowich and E.P. Osehobo (1997) Evidence against volume regulation by cortical brain cells during acute osmotic stress.  Exptl. Neurology. 143, 300-312.
 
Polischuk, T.M. and R.D. Andrew (1996)  Real time imaging of intrinsic optical signals during early excitotoxicity evoked by domoic acid in the hippocampal slice. Canad. J. Physiol. Pharm. 74,712-722.
 
Andrew, R.D., J.R. Adams and T.M. Polischuk (1996)  Imaging NMDA- and kainate- induced intrinsic optical signals from the hippocampal slice.  J. Neurophysiology 76, 2707-2717.
 
 
 
RECENT ABSTRACTS
 
Gagolewicz PJ and Andrew RD (2017) The elusive channel driving ischemic spreading depolarization. Society for Neuroscience, United States

Mehder RH, Petrin D, Gagolewicz PJ, Bennett BM, Jin AY, Andrew RD (2017) Survival of pyramidal neurons within the ischemic core of 12-hour post-MCAo mice. Society for Neuroscience, United States

Lowry C, Golod M, Bennett BM, Andrew RD (2017) Neuroprotection and differential Na+/K+ pump isoform expression in higher and lower brain regions. Canadian Assoc Neuroscience. Montreal PQ
 
Andrew RD, Hsieh Y-T and Brisson.CD (2016) Spreading depression is weak or absent in the rodent lower brain. Canadian Association for Neuroscience 2016, Toronto, Canada
 
Gagolewicz PJ and Andrew RD. (2016) Still unidentified: The channel driving spreading depolarization during ischemia. Canadian Association for Neuroscience 2016, Toronto, Canada
 
El-Kerdawy H, Carr J and Andrew RD. (2016) Mechanisms underlying neuronal swelling during acute osmotic or acute ischemic stress. Canadian Association for Neuroscience 2016, Toronto, Canada
 
Andrew RD. (2015) Spreading Depression and Migraine Pain as Evolutionary Epiphenomena of TBI. Co-operative Studies on Brain Injury Depolarizations 2015, Copenhagen, Denmark
 
 Brisson CD, Andrew RD. (2014) Spreading depolarization strength during ischemia determines higher brain susceptibility and lower brain resistance to acute injury. Society for Neuroscience 2014, Washington, United States
 
Andrew RD and Kim.D (2014) Does ischemia induce spreading depolarization by converting the Na+/K+ pump into a channel? Co-operative Studies on Brain Injury Depolarizations 2014, Boston, United States
 
Andrew RD. (2014) Spreading depolarization strength during ischemia determines higher brain susceptibility and lower brain resistance to acute injury. Workshop on Cortical Spreading Depression and Related Neurological
  1. Toronto, Canada
 
Andrew RD, Britton R, McQueen SA, Kim D, Jin AY  (2013)  Could the failing Na+/K+ pump convert to a channel during strokeSoc Neurosci Abstracts 2013
 
Andrew RD and Brisson CD (2013) Single neuron properties promote onset of the persistent vegetative state. Canad Assoc Neurosci  2013. Toronto
 
Petrin D, Ventura NM,  Peterson N, Andrew RD, Tse MY, Pang SC,Jin AY (2013)  Spreading depolarization is attenuated post-stroke and may involve isoform-specific altered sodium-potassium ATPase function. Canad Assoc Neurosci  2013. Toronto
 
Petrin D, Ventura NM,  Peterson N, Andrew RD, Tse MY, Pang SC,Jin AY (2013)  Spreading depolarization after stroke is supported by the alpha-1 isoform of Na+/K+-ATPase. Canadian Stroke Congress,  Montreal.
 
Ventura NM, Peterson NY, Tse MY, Wong PG, Jin AY, Andrew RD, Pang SC (2013)  Molecular effects of salt-induced hypertension on the development of acute ischemic stroke in the heterozygous ANP+/- gene-disrupted mice. Canadian Stroke Congress,  Montreal.
 
Petrin D, Andrew RD, Jin AY (2013) Endogenous and exogenous alteration of spreading depolarization in the post-stroke brain.  European Stroke Conference 2013.
 
Ventura NM, Peterson NT, Tse MY, Jin AY, Andrew RD, Pang SC. (2013) A novel model for ischemic stroke–the ANP gene disrupted (ANP−/−) mouse: molecular effects of hypertension in the development of stroke.  Exper Biol `13.
 
Andrew RD, Hsieh Y-T, Brisson  CD (2012) Projection neurons in brainstem and hypothalamus intrinsically resist acute stroke injury while projection neurons in cortex, striatum and thalamus die. .Soc Neurosci Abstracts 2012
 
Brisson  CD, Hsieh Y-T, Andrew RD (2012) Robust neuronal resistance to acute ischemic depolarization and swelling in midbrain-pons assessed with intracellular electrophysiology and two-photon microscopy. Soc Neurosci Abstracts 2012
 
Foreman-Mackey A., Peterson, N., Andrew, RD, Kaur, J., Singh, S., Jin, AY (2011) Acute stroke opens neuronal pannexin1 channels. Int. Stroke Conf., New Orleans, Feb 2012.
 
Andrew, RD, CD Brisson (2011) Trauma trumps stroke: Why is our higher brain inept at dealing with blocked blood flow? Vasospasm 2011: The 11th International Conference on Neurovascular Events after Subarachnoid Hemorrhage. Cincinatti, Ohio.
 
Brisson CD, Andrew RD (2011) Brainstem neurons in solitary nucleus resist ischemic stress compared to cortical pyramidal neurons. Soc. Neurosci. Abstr. 2011.
 
Andrew, R D (2010) When does `personhood`begin? Understanding neural development can inform the abortion issue. Neuroethics Society.
 
Pang, S. C., C.W. Reifel, L.W. MacKenzie, R.A. Easteal, R.D. Andrew, R.E. Hunt, S. Virk. (2010) Establishment of an internet-accessible, scalable gross anatomy and histology image catalogue (SGAHIC) for modern medical and health science education. Annual meeting of the Canadian Health Libraries Association.
 
Brisson, D.C., R. D. Andrew (2010) Magnocellular neuroendocrine cells dramatically resist stroke-like injury in live brain slices compared to neocortical pyramidal neurons. Soc. Neurosci. Abstr. 2010.
 
Ranepura N, C.D. Brisson and R. D. Andrew (2010) Neurons that resist osmotic volume change in brain slices and when dissociated. Soc. Neurosci. Abstr. 2010.
 
Brisson, D.C., N. Ranepura, M. Lukewich, R. D. Andrew (2009) Anoxic depolarization in hypothalamic and brainstem slices. Soc. Neurosci. Abstr.2009.
 
Andrew, R. D. (2008)   When does `personhood` begin? Teaching how neural development might inform the abortion issue.   Soc. Neurosci. Abstr.
White, S. H. and R. D. Andrew (2008) Whole cell recording from CA1 neurons to explain ischemia protection by dibucaine and carbetapentane. Soc. Neurosci. Abstr.
Andrew, R. D., W.C. Risher and S.A. Kirov (2008)  Real-time volume responses of astrocytes to osmotic and ischemic stressing vivo and in cortical slices revealed by 2-photon microscopy.  Canadian Physiological Society Meetings, Lake Louise, Alberta.
 
White, S. H. and R. D. Andrew (2008) Whole cell recording from pyramidal neurons help explain ischemia protection by a sodium channel blocker. Canadian Physiological Society Meetings, Lake Louise, Alberta.
 
Kirov, S. A. and R. D. Andrew, (2007) Real-time volume responses of astrocytes to osmotic and ischemic stress in cortical brain slices. Canad. J. Neurolog. Sci. 34 (Suppl 3), S67.
 
Andrew, R.D. and S. A. Kirov (2007) Two photon microscopy reveals real-time volume responses by astrocytes to osmotic and ischemic stress. Canadian Physiological Society Meetings, Quebec City, P.Q.
 
 
 
Scott, C.A., R. D. Andrew, J. P. Rossiter, and A. C. Jackson (2007) Marked injury to neuronal processes in an experimental mouse model of rabies using YFP transgenic mice.    ACV?
 
Kirov, S. A. and Andrew, (2006) CNS neurons withstand osmotic but not ischemic stress. The 50th Biophysical Society Annual Meeting, Salt Lake City, Utah
 
Andrew, R.D. S. E. Boehnke and S. A. Kirov (2006) Physiological evidence that pyramidal neurons lack water channels.  Canadian Physiological Society Meetings, Lake Louise, Alberta
 
Douglas, H.A., G. Yang, R. D. Andrew and S. A. Kirov  (2006) Two-photon microscopical study of pyramidal neurons protected from ischemic stress by dibucaine. Soc. Neurosci. Abstr. 2006
 
Kirov, S.A., S. E. Boehnke and R. D. Andrew (2006)  Real-time volume responses of astrocytes to osmotic and ischemic stress in cortical brain slices. Soc. Neurosci. Abstr. 2006
 
 
 
RESEARCH SUPPORT
 
RECENT FUNDING
 
NSERC Operating Grant. Converting the Na/K pump into a shutdown channel. Funded 2017 to 2022, $26K  per year. 
 
Heart and Stroke Foundation of Ontario Operating Grant.  “Higher brain susceptibility and lower brain resiliency to ischemic injury.”  Funded July 2014-June 2017
 
Gibson Award from Kingston General Hospital,  June  2015.    $9,000.
 
Dean`s Award in support of graduate student Steven Williams, September 2015.   $10,000.
 
Heart and Stroke Foundation of Ontario Operating Grant. “Mechanisms that drive acute neuronal swelling and dysfunction in stroke.”  July 2009 - June 2012.
 
Heart and Stroke Foundation of Ontario Operating Grant.  “Imaging and preventing early stroke damage in intact neurons.” July 2006 - June 2009.
 
CIHR Operating Grant. “Neuronal damage and potential protection in the first critical minutes of head trauma”. Funded Oct. 2004- Sept.2007.
 
Pending
 
- Request for operating funds to the Canadian Heart and Stroke Foundation, August 2017.    Resubmission August 2018.
- Request for operating funds to the CIHR, September 2017. Resubmission September 2018
 
 
 
RECENT INVITED Symposia Participation
 
February 12-16, 2018  Lecture: ‘A Putative Channel Driving Spreading Depolarization’.  Invited Workshop "Mathematical Modeling of Cortical Spreading Depression and Related Phenomena,” held at the Institute for Mathematics and its Applications. Minneapolis, USA.
April 2018.CBC Radio interview on the hazards of the poison Palytoxin.
 
July 2016.  York University, Toronto Ontario. Our brain: Wired for God and Country. Biology Dept. seminar. May 2016.
 
 
July 2014. International Workshop Speaker.  Cortical Spreading Depression and Related Neurological Phenomena.  Fields Institute, University of Toronto.
 
October 2014.  Speaker. Cooperative Studies on Brain Injury Depolarization Annual meeting. Boston MA.
 
 
 
RECENT INVITED LECTURES
 
December 2013. University of Arizona, Dept. of Basic Medical Sciences. Why is our brain so inept at dealing with blocked blood flow?
 
December 2013. University of North Texas.  Dept of Pharmacology and Neuroscience. Why is our brain so inept at dealing with blocked blood flow?
 
Sept  2013. One-On-One Debate: "How Can Neurobiology Inform the Political Issue of Personhood?"       Aggiornamento Institute, Colorado State University.
 
  
Graduate Supervision
 
Currently supervising one post-doc, two doctoral students, two MSc students and three fourth-year project students.
 
Graduated a total of 6 doctoral students and 24 MSc students.
 
Supervised 26 fourth-year project students.
 
 
 
 
TEACHING (2017-2018) 
 
ANAT 312/812*                    Functional Neuroanatomy
NSCI 429/829*                     Disorders of the Nervous System - Course Coordinator
NSCI 499                              Research Project in Neuroscience
NSCI 444/844*                     Controversies in Neuroscience - Course Coordinator  
                               
 
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.