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Which Spreading Depolarizations Are Deleterious To Brain Tissue?

  • C. William ShuttleworthEmail author
  • R. David Andrew
  • Yama Akbari
  • Cenk Ayata
  • Ramani Balu
  • K. C. Brennan
  • Martyn Boutelle
  • Andrew P. Carlson
  • Jens P. Dreier
  • Martin Fabricius
  • Eszter Farkas
  • Brandon Foreman
  • Raimund Helbok
  • Nils Henninger
  • Sharon L. Jewell
  • Stephen C. Jones
  • Sergei A. Kirov
  • Britta E. Lindquist
  • Carolina B. Maciel
  • David Okonkwo
  • Katelyn M. Reinhart
  • R. Meldrum Robertson
  • Eric S. Rosenthal
  • Tomas Watanabe
  • Jed A. Hartings
Proceedings
  • 168 Downloads

Abstract

Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of “Which SDs are deleterious to brain tissue?” iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions.

Keywords

Spreading depression Spreading depolarization Ischemia Trauma Subarachnoid hemorrhage 

Notes

Acknowledgements

We thank the Neurocritical Care Society and also thank the iCSD meeting sponsors: Moberg ICU Solutions, Raumedic, Hemedex, Integra, Natus, Nihon Kohden, Philips, Ad-Tech, Neurovisio, Perimed, Moor Instruments, PMT Corporation, Glia Media, and UC Gardner Neuroscience Institute. We thank Chanju D Fritch for assistance with documenting and preparing a transcript of the session. Authors’ work on this topic was supported by grants from NIH (NS106901, P20GM109089 (CWS); K23NS105950, U54NS100064 (ER); EB024793, CTSA Pilot Grant (subaward of UL1 TR001414), TR000147 (YA); NS102978 and NS104742 (KCB); K08NS091499 (NH), NS092181 (SCJ); T32 HL007736 (KMR); NS083858 (SAK); The Welcome Trust (MGB); Medical Research Council, UK (SJ); No. GINOP-2.3.2-15-2016-00048 (EF); DFG DR 323/5-1, DFG DR 323/10-1, FP7 no 602150 CENTER-TBI (JPD); Department of Defense: W81XWH-BAA-15-1, W81XWH-18-DMRDP-PTCRA, Moberg ICU Solutions subcontract, Office of the Assistant Secretary of Defense for Health Affairs, through the Defense Medical Research and Development Program under Award No. W81XWH-16-2-0020 (JAH); Discovery Grants from NSERC Canada (MR, RDA) and the Stroke Foundation of Canada (RDA). Claude D. Pepper Older Americans Independence Center (CBM). Opinions, interpretations, conclusions, and recommendations are solely those of the authors and are not necessarily endorsed by the Department of Defense or the National Institutes of Health.

Author’s Contribution

All authors contributed to the discussion session at the 2018 iCSD meeting that formed the basis of the manuscript. C.W.S. drafted the manuscript based on a transcript from the discussion session. All authors provided feedback and revisions that were incorporated into the final document.

Conflict of interest

Dr. Henninger serves on the advisory board of Omniox, Inc. and serves as consultant to Astrocyte Pharmaceuticals, Inc.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2019

Authors and Affiliations

  • C. William Shuttleworth
    • 1
    • 32
    Email author
  • R. David Andrew
    • 2
  • Yama Akbari
    • 3
  • Cenk Ayata
    • 4
  • Ramani Balu
    • 5
  • K. C. Brennan
    • 6
  • Martyn Boutelle
    • 7
  • Andrew P. Carlson
    • 8
  • Jens P. Dreier
    • 9
    • 10
    • 11
    • 12
    • 13
  • Martin Fabricius
    • 14
  • Eszter Farkas
    • 15
  • Brandon Foreman
    • 16
    • 27
    • 29
    • 30
  • Raimund Helbok
    • 17
  • Nils Henninger
    • 18
  • Sharon L. Jewell
    • 19
  • Stephen C. Jones
    • 20
  • Sergei A. Kirov
    • 21
    • 22
  • Britta E. Lindquist
    • 23
  • Carolina B. Maciel
    • 24
  • David Okonkwo
    • 31
  • Katelyn M. Reinhart
    • 1
  • R. Meldrum Robertson
    • 25
  • Eric S. Rosenthal
    • 26
  • Tomas Watanabe
    • 28
  • Jed A. Hartings
    • 16
    • 29
    • 30
  1. 1.Department of NeurosciencesUniversity of New Mexico School of MedicineAlbuquerqueUSA
  2. 2.Department of Biomedical and Molecular SciencesQueen’s UniversityKingstonCanada
  3. 3.Department of NeurologyUniversity of CaliforniaIrvineUSA
  4. 4.Neurovascular Research Laboratory, Department of Radiology, Massachusetts General HospitalHarvard Medical SchoolCharlestownUSA
  5. 5.Department of Neurology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  6. 6.Department of NeurologyUniversity of Utah School of MedicineSalt Lake CityUSA
  7. 7.Department of BioengineeringImperial College LondonLondonUK
  8. 8.Department of NeurosurgeryUniversity of New Mexico School of MedicineAlbuquerqueUSA
  9. 9.Department of NeurologyCharité – Universitätsmedizin Berlin, corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  10. 10.Bernstein Center for Computational Neuroscience BerlinBerlinGermany
  11. 11.Einstein Center for Neurosciences BerlinBerlinGermany
  12. 12.Center for Stroke Research BerlinCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  13. 13.Department of Experimental NeurologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  14. 14.Department of Clinical NeurophysiologyRigshospitaletCopenhagenDenmark
  15. 15.Department of Medical Physics and Informatics, Faculty of MedicineUniversity of SzegedSzegedHungary
  16. 16.Department of NeurosurgeryUniversity of Cincinnati (UC) College of MedicineCincinnatiUSA
  17. 17.Department of Neurology, Neurocritical CareMedical University of InnsbruckInnsbruckAustria
  18. 18.Departments of Neurology and PsychiatryUMass Medical SchoolWorcesterUSA
  19. 19.Department of Basic and Clinical NeuroscienceKing’s CollegeLondonUK
  20. 20.CerebroScopePittsburghUSA
  21. 21.Department of Neuroscience and Regenerative Medicine, Medical College of GeorgiaAugusta UniversityAugustaUSA
  22. 22.Department of Neurosurgery, Medical College of GeorgiaAugusta UniversityAugustaUSA
  23. 23.Department of NeurologyUniversity of CaliforniaSan FranciscoUSA
  24. 24.Department of NeurologyUniversity of FloridaGainesvilleUSA
  25. 25.Department of BiologyQueen’s UniversityKingstonCanada
  26. 26.Department of NeurologyMassachusetts General HospitalBostonUSA
  27. 27.Department of Neurology and Rehabilitation MedicineUniversity of Cincinnati (UC) College of MedicineCincinnatiUSA
  28. 28.Vagalume LLCPalo AltoUSA
  29. 29.Collaborative for Research on Acute Neurologic InjuryUniversity of Cincinnati (UC) College of MedicineCincinnatiUSA
  30. 30.UC Gardner Neuroscience InstituteCincinnatiUSA
  31. 31.Department of Neurological SurgeryUniversity of PittsburghPittsburghUSA
  32. 32.Department of Neurosciences, MSC08 47401 University of New MexicoAlbuquerqueUSA

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