Cajal course on Brain Homeostasis and Neurovascular Coupling files/CAJAL/2019... · Cajal course on Brain Homeostasis and Neurovascular Coupling Instructors Jerome Badaut, PhD

The CAJAL Advanced Neuroscience Training Programme www.cajal-training.org

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Cajal course on

Brain Homeostasis and Neurovascular Coupling

Instructors

Jerome Badaut, PhD (Brain Molecular Imaging Lab, INCIA, University of Bordeaux) Biosketch: Jerome Badaut’s laboratory is currently investigating the roles of the astrocyte-endothelium-neuron interactions within the neurovascular unit in pathological processes after traumatic brain injury and stroke. His goal is to use the enhanced understanding of functional and molecular changes in the neurovascular unit after injury to generate new target-specific drugs to promote functional recovery of individuals affected by brain injury. Investigations of

molecular mechanisms are performed in preclinical models with the use of several appraoches such as behavioural testing paradigms, magnetic resonance imaging, histological and molecular biology techniques. Dr Badaut sets a unique international expertise on the role of the aquaporin (water channel) in brain edema processes post-injury and on the longterm blood vessel phenotypic changes after pediatric traumatic brain injury . Dr Badaut has been able to maintain active laboratory in several institutions, first in Lausanne University (Switzerland), then in Loma Linda University (CA, USA), before to be appointed senior research officer at the National Center for Scientific Research (CNRS) at Bordeaux Neurocampus. Dr. Badaut recently edited a book on Brain edema7 and he is associated editor of Journal of Neuroscience Research.

Selected publications:

Jullienne, A., et al. Modulating the water channel AQP4 alters miRNA expression, astrocyte connectivity and water diffusion in the rodent brain. Sci Rep 8, 4186 (2018) Rodriguez-Grande, B., et al. Gliovascular changes precede white matter damage and long-term disorders in juvenile mild closed head injury. Glia (2018) Badaut, J. and Plesnila, N. Brain edema. From Molecular Mechanisms to Clinical Practice. Academic Press (2017)


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Björn Bauer, PhD (College of Pharmacy, University of Kentucky) Biosketch: Björn Bauer is Associate Professor of Pharmaceutical Sciences in the College of Pharmacy. He received a BS in Pharmacy in 1997 and a PhD in Pharmaceutical Sciences/Pharmacology in 2002 from the University of Heidelberg, Germany. From 2002-2007, Dr. Bauer was Postdoctoral Fellow at the NIH/NIEHS in Research Triangle Park, NC, and in 2007 was appointed Assistant Professor at the University of Minnesota College of Pharmacy. In 2014, Dr. Bauer joined the University of Kentucky College of Pharmacy, where his research is

focused on the regulation of blood-brain barrier function in brain disorders, specifically epilepsy, Alzheimer’s disease, and brain cancer. Dr. Bauer’s research is funded by several NIH grants.


Rempe RG, Hartz AMS, Soldner ELB, Sokola BS, Alluri SR, Abner EL, Kryscio RJ, Pekcec A, Schlichtiger J, Bauer B. Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy. Journal of Neuroscience. 38(18):4301-4315 (2018) Hartz AM, Zhong Y, Wolf A, LeVine H 3rd, Miller DS, Bauer B. Aβ40 Reduces P-Glycoprotein at the Blood-Brain Barrier through the Ubiquitin-Proteasome Pathway. Journal of Neuroscience. 36(6):1930-1941 (2016) Hartz AM, Schulz JA, Sokola BS, Edelmann SE, Shen AN, Rempe RG, Zhong Y, Seblani NE, Bauer B. Isolation of Cerebral Capillaries from Fresh Human Brain Tissue. Journal of Visualized Experiments. (139), e57346 (2018)


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Jason Berwick, PhD (Department of Psychology, The University of Sheffield) Biosketch: I am a neuroscientist investigating a mechanism called neurovascular coupling in the brain. Neurovascular coupling ensures that active regions of the brain receive enough glucose and oxygen to function and also provides the main contrast mechanism for functional magnetic resonance imaging. My research interests are to investigate how neurovascular coupling is changing in disease and ageing using pre-clinical rodent animal models. My recent research has focussed on the investigation neurovascular breakdown in Alzheimer’s Disease and

focal cortical epilepsy.


Harris S, Boorman L, Kennerley AJ, Sharp P, Martin C, Redgrave P, Schwartz T, Berwick J (2018) Seizure epicenter depth and translaminar field potential synchrony underlie complex variations in tissue oxygenation during ictal initiation. NeuroImage 171:165-175 Sharp PS, Shaw K, Boorman L, Harris S, Kennerley AJ, Azzouz M, Berwick J. (2015). Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime. Scientific Reports 12621 doi:10.1038/srep12621 Boorman L, Harris S, Bruyns-Haylett M, Kennerley A, Zheng Y, Martin C, Jones M, Redgrave P, Berwick J (2015). Long-latency reductions in gamma power predict hemodynamic changes that underlies the negative BOLD signal. Journal of Neuroscience 18. 35(11): 4641-4656


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Craig Brown, PhD (Division of Medical Sciences, University of Victoria) Biosketch: Dr. Craig Brown is an Associate Professor in the Division of Medical Sciences at the University of Victoria. One of his primary research interests is to understand the cellular and molecular mechanisms that dictate brain repair, with particular emphasis on stroke and/or vascular diseases such as diabetes. To address these questions, the Brown lab employs a multi-disciplinary approach, imaging the structure and function of defined cell types (neurons, microglia, endothelial cells) of the living brain in tandem with biochemical,

pharmacological and behavioural approaches. Since starting his laboratory in 2009, Dr. Brown’s basic science and health related research program has been supported by the Canadian Institute for Health Research (CIHR), Heart and Stroke Foundation of Canada, and NSERC. Dr. Brown is also a recipient of the CIHR New Investigator award and the Michael Smith Foundation’s Career Investigator Award.


Taylor S, Mehina E, White E, Reeson P, Youngblah K, Doyle K, Brown CE. 2018. Suppressing interferon gamma stimulates microglial responses and repair of cerebral microbleeds in the diabetic brain. Journal of Neuroscience 38(40): 8707-8722 Reeson P, Choi K, Brown CE. 2018. VEGF signalling regulates the fate of obstructed cortical capillaries. eLife Apr 26;7. pii: e33670. doi: 10.7554/eLife.33670 Tennant KA, Taylor S, White E, Brown CE. 2017. Optogenetic rewiring of thalamocortical circuits to restore function in the stroke injured brain. Nature Communications Jun 23;8:15879. doi: 10.1038/ncomms15879


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Hélène Girouard, PhD (Department of pharmacology and physiology, Université de Montréal) Biosketch: Dr Girouard completed her PhD in cardiovascular physiology in 2002 at the Université de Montreal under the supervision of Dr J. de Champlain, a specialist in the field of hypertension. She then pursued with two fellowships both on the study of cerebrovascular regulation: one at the Weill Medical College of Cornell University and a second one at the University of Vermont under the supervisions of Dr. Costantino Iadecola and Dr Mark T. Nelson, respectively. She is now associate professor at the Department of

pharmacology and physiology at the Université de Montréal and the director of the laboratory of neurovascular pharmacology since 2008. Along her career, Dr Girouard received prices including the Merck New investigator price of the ‘Société Québécoise d’Hypertension Artérielle’ and the Young Investigator Award from the Heart and Stroke Foundation of Canada. She recently was nominated Fellow of the American Heart Association. She is involved in many Societies related to Hypertension and neurosciences in particular the ‘Société Québécoise d’Hypertension Artérielle’ and the ‘International Society of Cerebral Blood Flow and Metabolism’ in which she is member of the Board of Directors. The research interests of Dr Girouard are the study of the mechanisms underlying cerebrovascular regulation in health and diseases especialy in the context of hypertension and arterial stiffness. The main objective of her research is to find therapeutical targets to protect the brain from vascular diseases. To reach this objective, she is using various techniques from molecular biology to brain imaging in mice and humans. She published mostly in the field of hypertension and cerebrovascular regulation.


Iulita MF, Vallerand D, Beauvillier M, Haupert N, Ulysse CA, Gagné A, Vernoux N, Duchemin S, Boily M, Tremblay ME, Girouard H. Differential effects of angiotensin II and blood pressure on hippocampal inflammation in mice. J. Neuroinflammation. 2018; 15(1):62 Bloch S, Obari D, Girouard H, Angiotensin and neurovascular coupling: beyond hypertension. Microcirculation. 2015 Girouard H, Bonev A, Hannah R, Meredith A, Aldrich R, Nelson MT. Astrocytic endfoot calcium and BK channels determine cerebrovascular dilation and constriction during neurovascular coupling. PNAS 2010


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Viki Hurst, PhD (UK National Centre for the Replacement, Refinement and Reduction of animals in research)

Biosketch: Dr Hurst is a Science Manager at the UK National Centre for the Replacement, Refinement and Reduction of animals in research, working on a programme designed to improve experimental design and the quality of reporting of animal research. This includes development of the Experimental Design Assistant, an online tool to guide researchers through the design of in vivo experiments, and dissemination of the Animal Research: Reporting In Vivo Experiments (ARRIVE) Guidelines. Dr Hurst is

currently leading efforts with an expert international working group made up of in vivo researchers, statisticians and reporting guideline developers to increase the uptake of the ARRIVE guidelines. This work will produce an up-to-date revision of the guidelines, more accessible resources, and an accompanying explanations and elaborations publication to help researchers understand key concepts in the reporting of animal research. She was awarded a PhD in the field of Cognition, Behaviour and Pharmacology in animal models of Affective Disorders from Newcastle University (UK), and worked as a postdoctoral researcher investigating novel therapeutics in a rat model of Cancer-Induced Bone Pain at the University of Sheffield (UK).


Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Altman, D. G., Avey, M. T., . . . Holgate, S. T. (2018). Revision of the ARRIVE guidelines: rationale and scope. BMJ Open Science, 2(1). Percie du Sert N, Bamsey I, Bate ST, Berdoy M, Clark RA, Cuthill I, Fry D, Karp NA, Macleod M, Moon L, Stanford SC, Lings B (2017) The Experimental Design Assistant. PLoS Biol 15(9): e2003779. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research. PLoS Biol 8(6): e1000412.


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Changsi Cai, PhD (Department of Neuroscience, University of Copenhagen, Denmark) Biosketch:

When I was PhD student, I was in a joint project between Shanghai Jiao-Tong University and Harvard University, working with artificial retina to restore vision for the blinds. I am currently a postdoc at Department of Neuroscience, University of Copenhagen, Denmark. I am working with Professor Martin Lauritzen, in the field of regulation of cerebral blood flow. My main research interest are conducted vascular responses (CVRs) in cerebral capillaries, mechanism of blood flow regulation, signaling between astrocytes and pericytes. My skill set includes patch clamp, two-photon microscopy, viral vector injection, MATLAB program.


-Cai C., Fordsmann J. C., Jensen S. H., Gesslein B., Lonstrup M., Hald B. O., Zambach S. A., Brodin B., Lauritzen M. J. Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses. Proc Natl Acad Sci (PNAS) USA 2018, 115(25): E5796-E5804. -Jimenez E., Cai C., Mikkelsen I., Rasmussen P., Angleys H., Merrild M., Mouridsen K., Jespersen S., Lee J., Iversen N., Sakadzic S., Østergaard L. Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH).Journal of Cerebral Blood Flow & Metabolism. 2016, 36.12: 2072-2086. -Cai, C., Twyford, P., & Fried, S. The response of retinal neurons to high-frequency stimulation. J. Neur. Eng. 2013, 10(3), 036009.


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Krzysztof Kucharz, PhD (Department of Neuroscience, University of Copenhagen, Denmark) Biosketch: Krzysztof Kucharz, 39, is an Assistant Professor at the Department of Neuroscience, University of Copenhagen, Denmark specializing in brain homeostasis and two-photon imaging. He obtained his BSc and MSc at the Institute of Molecular Biology, Department of Biophysics, Krakow, Poland investigating how the molecular guardians of the cell, the heat shock proteins, can maintain their protective role in conditions where ATP is scarce. Following that, he worked as an intern and later research assistant at Lund

University and Uppsala University, Sweden in the biotech companies Everygene and Olink where he helped develop ultra-sensitive molecular probes for detection of aberrant proteins in human blood and other tissues. This was when live fluorescence microscopy became the main part of Krzysztof’s work and interest. He began his PhD in Neuroscience at Faculty of Medicine, Lund University, Sweden focusing on cellular stress mechanisms using live cell/tissue/brain imaging of neuronal organelle dynamics in physiology and disease. His work revealed that neuronal endoplasmic reticulum undergoes rapid, reversible and repeatable fission – a process with great implications for brain calcium homeostasis and neurotransmission. Following his research interests and the method of choice, i.e. two-photon in vivo imaging, Krzysztof joined Martin Lauritzen’s lab at University of Copenhagen, Denmark in 2012. There, as a post-doc and later Assistant Professor, he further explored neuronal organelle responses in vivo, this time utilizing sophisticated pharmacological modulators, including novel compounds that can penetrate the blood brain barrier (BBB). This sparked Krzysztof’s interest in the BBB and design of drug delivery systems and his current research is focused on cell-penetrating peptides (CPPs) and antibody-targeted liposome drug nanocarriers. In his work, Krzysztof investigates pharmacokinetics of custom-made CPPs and nanoliposomes and their spatio-temporal profiles in the CNS, i.e. permeability, distribution, and accumulation patterns at the BBB in brain parenchyma. Krzysztof is a part of the Research Initiative on Brain Barriers and Drug Delivery and his goal is to pinpoint specific cellular mechanisms in the BBB that can be modulated for increased drug delivery to the brain.


Kucharz, K., et al. CaMKII-dependent endoplasmic reticulum fission by whisker stimulation and during cortical spreading depolarization. Brain. (2018) Kucharz, K., et al. PSD-95 uncoupling from NMDA receptors by CPP Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression. J Cereb Blood Flow Metab. (2016)


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Kucharz, K., et al. 2013. Fission and fusion of the neuronal endoplasmic reticulum. Trans. Stroke Res. (2013)


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Nikolay Kutuzov, PhD (Department of Neuroscience, University of Copenhagen, Denmark) Biosketch: As an undergraduate student, Nikolay studied the properties of myelin with optical methods. With Raman spectroscopy he showed that properties of myelin vary within single nerve fibers and change in response to purinergic signalling molecules. As a graduate student, Nikolay studies the microstructure of the blood-brain barrier (BBB) to understand how its components affect the transport of molecules from blood to brain. He developed methods to analyze the barrier properties of the endothelial glycocalyx and

astrocyte endfeet in vivo and showed how these structures enhance the BBB.


Kutuzov N. et al. (2015), Journal of Biomedical Optics 20(5):50501 Kutuzov N. et al. (2015), PLoS One 10(11): e0142084 Kutuzov N. et al. (2018), PNAS 115(40): E9429-E9438


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Clotilde Lecrux, PhD (Cerebrovascular Laboratory, Montreal Neurological Institute, McGill University, Montréal, QC, Canada)

Biosketch: I am a Research Associate at McGill University, working with Dr Edith Hamel, I am leading the in vivo neurovascular coupling (NVC) experiments. While my PhD was on cerebral ischemia, I have subsequently focussed on the mechanisms of NVC, aiming to identify the cellular and molecular cascades of communication between neurons and brain blood vessels. I have studied NVC pathways recruited in the cerebral cortex following activation of a glutamatergic sensory input and the basal forebrain cholinergic

pathway. I collaborated to the characterization of the role of prostaglandins and their receptors in sensory-evoked NVC responses (1). As presented in our recent review (2), we also aim to elucidate the effects of altered brain states on NVC, as driven by varying cholinergic tones (3). Overall, my expertise involves in vivo investigation of NVC, combining electrophysiology (local field potentials) and hemodynamic signals (cerebral blood flow by laser-Doppler flowmetry and laser speckle contrast imaging, and hemoglobin levels by optical imaging of intrinsic signals) in anesthetized and awake mice. I am also investigating the role of modulatory pathways in altering sensory-evoked NVC responses, using either pharmacological or optogenetic manipulation of targeted neuronal populations.


Lacroix et al. (2015) J Neurosci 35(34):11791-810 Lecrux et Hamel (2016) Philos Trans R Soc Lond B Biol Sci 371(1705) Lecrux et al. (2017) J Neurosci 37(6):1518-1531


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Søren Grubb, PhD (Department of Neuroscience, University of Copenhagen, Denmark) Biosketch:

I am a biologist with special interest in fluorescence imaging and electrophysiology. My research focuses on blood regulation in the brain with special interest in the role of contractile cells surrounding the blood vessels. I have been working with neuroscience for two years now in Martin Lauritzen lab, but my background is in cardiac research and ion channel research. My current research focuses on the role of pericytes and smooth muscle cells in blood flow regulation in the brain.

My scientific focuses are: Precapillary sphincters: Investigating the role of precapillary sphincters in cerebral blood flow regulation Red blood cell flow: Measuring RBC velocity and flux using resonance scanning. Ca2+dynamics: Intracellular Ca2+homeostasis, irregularities and response to stimuli. Ion channels: Investigating and characterizing ion currents and electrical properties of cells.


-Grubb S, Vestergaard ML, Andersen AS, Rasmussen KK, Mamsen L, Tuckute G, Grunnet-Lauridsen K, Møllgård K, Ernst E, Christensen ST, Calloe K and Andersen, CY. “Comparison of cultured human cardiomyocyte clusters obtained from embryos/fetuses or derived from human embryonic stem cells.” Stem Cells Dev. 2019. -Grubb S, Aistrup GL, Koivumäki JT, Speerschneider T, Gottlieb LA, Mutsaers NAM, Olesen SP, Calloe K, Thomsen MB. “Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2.” American Journal of Physiology, 2015 Aug 1. -Grubb S, Speerschneider T,Occhipinti D, Fiset C, Olesen SP, Thomsen M, Calloe K. “Loss of K+ Currents in Heart Failure Is Accentuated in KChIP2 Deficient Mice”. J Cardiovasc Elec. 2014;25:896-904. -Grubb S, Poulsen KA, Juul CA Kyed T, Klausen TK, Larsen EH, Hoffmann EK. "TMEM16F (Anoctamin 6), an anion channel of delayed Ca(2+) activation.". J Gen Physiol 2013;141:585-600.


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Kazuto Masamoto, PhD (Faculty of Informatics and Engineering, University of Electro-Communications, Tokyo, Japan / Department of Functional Brain Imaging Research, National Institute of Radiological Sciences (NIRS), Chiba, Japan)

Biosketch: Dr. Masamoto PhD. is currently Professor of the Brain Science Inspired Life Support Research center, Faculty of Informatics and Engineering at the University of Electro-Communications, Tokyo, Japan, and a Visiting Collaborative Researcher of the Department of Functional Brain Imaging Research at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. He received his Ph.D. in Engineering from Keio University (Prof. Kazuo Tanishita) and worked at University of Pittsburgh (Prof. Seong-Gi Kim) and NIRS (Prof. Iwao

Kanno). His major research interests include structural and functional plasticity of the neurovascular unit (NVU), specifically focusing on adaptive changes in brain microcirculation and neurovascular coupling regulations in healthy and diseased brains. He has published over 60 peer-reviewed papers. Dr. Masamoto received the Melvin H. Knisely Award from ISOTT in 2008, and has been Editorial Board of JCBFM since 2011, Director Board of ISCBFM since 2017, and served on the Program Committee for the Brain 2015 and co-chairs of the Program Committee for the Brain 2019.


Masamoto K, Vazquez A. Optical imaging and modulation of neurovascular responses. J Cereb Blood Flow Metab. 2018 Oct 18:271678X18803372. PMID: 30334644 Masamoto K, Unekawa M, Watanabe T, Toriumi H, Takuwa H, Kawaguchi H, Kanno I, Matsui K, Tanaka KF, Tomita Y, Suzuki N. Unveiling astrocytic control of cerebral blood flow with optogenetics. Sci Rep. 2015 Jun 16;5:11455. PMID: 26076820 Masamoto K, Takuwa H, Seki C, Taniguchi J, Itoh Y, Tomita Y, Toriumi H, Unekawa M, Kawaguchi H, Ito H, Suzuki N, Kanno I. Microvascular sprouting, extension, and creation of new capillary connections with adaptation of the neighboring astrocytes in adult mouse cortex under chronic hypoxia. J Cereb Blood Flow Metab. 2014 Feb;34(2):325-31. PMID: 24252848


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Anusha Mishra, PhD (Neurovascular Coupling lab, Knight Cardiovascular Institute, Oregon Health & Science University, Oregon, USA)

Biosketch: Anusha Mishra is interested in the physiological and pathological interactions between astrocytes and the cerebral microvasculature. Her past work investigated astrocyte regulation of retinal vasculature, where she discovered a drug that reverses the loss of neurovascular coupling in diabetic retinopathy1. She also demonstrated that astrocytes regulate capillary diameter in the cerebral cortex2, and that ischemia-induced capillary constriction might underlie the no-reflow phenomenon following

stroke. She further described the dichotomous pathways that regulate neurovascular coupling at capillaries and arterioles. She has also described the techniques to study pericyte regulation of capillary blood flow ex vivo3. She recently started her independent research group investigating the relationship between reactive astrocytes and neurovascular impairment after ischemic stroke and in dementia.


Mishra, A. & Newman, E. A. Aminoguanidine reverses the loss of functional hyperemia in a rat model of diabetic retinopathy. Front Neuroenergetics. 3, 10 (2011) Mishra, A. et al. Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles. Nat Neurosci (2016) Mishra, A. et al. Imaging pericytes and capillary diameter in brain slices and isolated retinae. Nat.Protoc. 9, 323-336 (2014)


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U. Valentin Nägerl, PhD (Interdisciplinary Institute for NeuroScience of the CNRS / University of Bordeaux)

Biosketch: Dr. U. Valentin Nägerl is a full professor of neuroscience and bio-imaging at the University of Bordeaux, where he directs the master’s program in cellular bio- imaging and heads a research team focusing on the structural mechanisms of synaptic plasticity by applying novel in vivo super-resolution microscopy approaches. He studied physics as an undergraduate student in Göttingen and obtained his PhD in neuroscience with Istvan Mody at UCLA. Dr. Nägerl worked as a postdoc and group leader with Tobias Bonhoeffer at the Max Planck

Institute of Neurobiology in Martinsried/Munich, obtained his habilitation in neuroscience under Arthur Konnerth at the Technical University of Munich and worked with the Nobel laureate Stefan W. Hell at the Max Planck Institute for Biophysical Chemistry. Dr. Nägerl is well-known for his work on STED microscopy and synaptic plasticity, and is frequently invited to speak at and organize international scientific conferences and symposia. He has been in charge of several collaborative research projects, received the prestigious ‘Equipe FRM’ award in 2016, became a member of the ‘Institut Universitaire de France’ in 2017 and won the ‘Great Advances in Biology’ prize from the French Academy of Sciences in 2018.


Hrabetova S, Cognet L, Rusakov DA, Nägerl UV. Unveiling the extracellular space of the brain: from super-resolved microstructure to in vivo function. J. Neurosci. 2018 38(44):9355–9363. Pfeiffer T, Poll S, Bancelin S, Angibaud J, Innavalli KVVG, Keppler K, Mittag M, Fuhrmann M, Nägerl UV, Chronic 2P-STED imaging reveals high turnover of dendritic spines in the hippocampus in vivo, Elife, 7, e34700 (2018) Tonnesen J, Inavalli KVVG, Nägerl UV, Super-resolution imaging of the extracellular space in living brain tissue, Cell, 172(5), 1108-1121 (2018)


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Andre Obenaus, PhD (Professor, Dept. of Pediatrics, University of California Irvine; Director, Preclinical and Translational Imaging Center)

Biosketch: Dr. Obenaus’ research interests include the use of novel magnetic resonance imaging approaches to non-invasively identify the evolution of neuropathology and how the brain responds to therapeutic interventions. His research investigates the influence of vascular alterations in brain trauma, non-invasive and predictive biomarkers relevant to febrile seizures and the subsequent development of epilepsy, use of human neural stem cells for the treatment of neonatal hypoxic ischemic brain injury, the evolution of

white matter loss in adult and juvenile brain following neurotrauma, and novel therapeutic compounds for mitigating the effects of stroke, among others. The use of automated computer vision techniques for analysis of biomedical data is a research interest. He has extensive collaborations with national and international researchers to compliment and extend these research endeavors.


Curran MM, Haddad E, Patterson KP, Choy M, Dubé CM, Baram TZ, Obenaus A. (2018) Epilepsy-predictive, magnetic resonance imaging changes following experimental Febrile Status Epilepticus: are they translatable to the clinic? Epilepsia, 1–14. DOI: 10.1111/epi.14561 Jullienne A, Salehi A, Affeldt B, Baghchechi M, Haddad E, Avitua A, Walsworth M, Enjalric I, Hamer M, Bhakta S, Tang J, Zhang J, Pearce WJ, Obenaus A. (2018) Male and female mice exhibit divergent responses of the cortical vasculature to traumatic brain injury. J Neurotrauma. 2018 Mar 5. doi: 10.1089/neu.2017.5547. [Epub ahead of print] Bolton JL, Molet J, Regev L, Chen Y, Rismanchi N, Haddad E, Yang DZ, Obenaus A, Baram TZ (2018) Anhedonia following early-life adversity involves aberrant interaction of reward and anxiety circuits and is reversed by partial silencing of amygdala corticotropin-releasing hormone gene. Biol Psychiatry. 2018 Jan 15;83(2):137-147. doi: 10.1016/j.biopsych.2017.08.023. Epub 2017 Sep 7


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William J. Pearce, PhD (Division of Physiology, Loma Linda University School of Medicine) Biosketch: William Pearce earned his PhD in Physiology at the University of Michigan in 1978, after which he completed his postdoctoral training in Pharmacology with John A Bevan at UCLA. He joined the Physiology faculty of the Loma Linda University School of Medicine in 1983, where he has held the rank of Professor since 1997. Beginning with his doctoral dissertation, Dr. Pearce’s research interests have focused on the vascular biology of cerebral arteries, with an emphasis on how both physiological and pathophysiological perturbations modulate

structure-function relations in the fetal cerebral circulation. This work has been continuously funded by the US National Institutes of Health for more than 30 years and has resulted in more than 165 peer-reviewed publications.


Durrant LM, Khorram O, Buchholz JN, and Pearce WJ. Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: effects of metyrapone. Am J Physiol Regul Integr Comp Physiol 306: R401-410, 2014. PMID: 24477541 Pearce WJ, Doan C, Carreon D, Kim D, Durrant LM, Manaenko A, McCoy L, Obenaus A, Zhang JH, and Tang J. Imatinib attenuates cerebrovascular injury and phenotypic transformation after intracerebral hemorrhage in rats. Am J Physiol Regul Integr Comp Physiol 311: R1093-R1104, 2016. PMID: 27707720 Silpanisong J, Kim D, Williams JM, Adeoye OO, Thorpe RB, and Pearce WJ. Chronic hypoxia alters fetal cerebrovascular responses to endothelin-1. Am J Physiol Cell Physiol 313: C207-c218, 2017. PMID: 28566491


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Ravi L. Rungta, PhD (Laboratory of Neurophysiology and New Microscopy, French Institute of Health and Medical Research (INSERM), Paris)

Biosketch: Ravi completed his PhD in Neurosciences at the University of British Columbia in the lab of Brian MacVicar. During his doctoral work he developed advanced methodology for imaging activity and silencing gene expression in neuronal and glial cells and delineated cellular mechanisms underlying cytotoxic neuronal edema. Ravi was then awarded an EMBO fellowship in the lab of Serge Charpak, where he is combining 2-photon and fast functional ultrasound imaging to investigate the spatial-temporal dynamics of neurovascular coupling.

The focus of his current research is aimed at linking synaptic activation to hemodynamic signals with the goal of better interpreting human brain imaging signals.


Rungta et al., (2015) Cell, 161(3):610-21 Rungta et al., (2017) Nature Communications, 8:14191 Rungta et al., (2018) Neuron, 99; 362–375


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Ulf Toelch, PhD (Quest Center for Transforming Biomedical Research) Biosketch: Ulf started his scientific career in behavioural biology and then switched for several post doc years to psychology and cognitive neuroscience. Now he is based at the QUEST Center for transforming

biomedical research educating medical and doctoral students in reproducible research practices. Beyond this, he is investigating reproducibility and its impact on the translational biomedical process. (for details see: https://orcid.org/0000-0002-8731-3530)


Toelch, U., Pooresmaeili, A., & Dolan, R. J. (2018). Neural substrates of norm compliance in perceptual decisions. Scientific Reports, 8(1), 3315. Toelch, Ulf, & Dolan, R. J. (2015). Informational and Normative Influences in Conformity from a Neurocomputational Perspective. Trends in Cognitive Sciences, 19(10), 579–589. Toelch, Ulf, Panizza, F., & Heekeren, H. R. (2018). Norm compliance affects perceptual decisions through modulation of a starting point bias. Open Science, 5(3), 171268.

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Cajal course on Brain Homeostasis and Neurovascular Coupling files/CAJAL/2019... · Cajal course on Brain Homeostasis and Neurovascular Coupling Instructors Jerome Badaut, PhD