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Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

Robert H. Wilson, Christian Crouzet, Donald E. Lee, Dishant P. Donga, Ayushi H. Patel, Afsheen Bazrafkan, Niki Maki, Masih A. Rafi, Maziar Moslehyazdi, Justin H. Pham, Mohammad Torabzadeh, Brooke E. Hjelm, Bruce J. Tromberg, Oswald Steward, Beth A. Lopour, Bernard Choi, Yama Akbari
doi: https://doi.org/10.1101/786210
Robert H. Wilson
1Beckman Laser Institute, University of California, Irvine, CA, USA
5Department of Biomedical Engineering, University of California, Irvine, CA, USA
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Christian Crouzet
1Beckman Laser Institute, University of California, Irvine, CA, USA
5Department of Biomedical Engineering, University of California, Irvine, CA, USA
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Donald E. Lee
2Department of Neurology, University of California, Irvine, CA, USA
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Dishant P. Donga
2Department of Neurology, University of California, Irvine, CA, USA
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Ayushi H. Patel
2Department of Neurology, University of California, Irvine, CA, USA
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Afsheen Bazrafkan
2Department of Neurology, University of California, Irvine, CA, USA
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Niki Maki
2Department of Neurology, University of California, Irvine, CA, USA
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Masih A. Rafi
2Department of Neurology, University of California, Irvine, CA, USA
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Maziar Moslehyazdi
2Department of Neurology, University of California, Irvine, CA, USA
5Department of Biomedical Engineering, University of California, Irvine, CA, USA
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Justin H. Pham
2Department of Neurology, University of California, Irvine, CA, USA
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Mohammad Torabzadeh
1Beckman Laser Institute, University of California, Irvine, CA, USA
5Department of Biomedical Engineering, University of California, Irvine, CA, USA
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Brooke E. Hjelm
3Department of Translational Genomics, University of Southern California, Los Angeles, CA, USA
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Bruce J. Tromberg
1Beckman Laser Institute, University of California, Irvine, CA, USA
5Department of Biomedical Engineering, University of California, Irvine, CA, USA
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Oswald Steward
4Reeve-Irvine Research Center, Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA, USA
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Beth A. Lopour
5Department of Biomedical Engineering, University of California, Irvine, CA, USA
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Bernard Choi
1Beckman Laser Institute, University of California, Irvine, CA, USA
5Department of Biomedical Engineering, University of California, Irvine, CA, USA
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Yama Akbari
1Beckman Laser Institute, University of California, Irvine, CA, USA
2Department of Neurology, University of California, Irvine, CA, USA
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  • For correspondence: yakbari@gmail.com
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Abstract

Spreading depolarization (SD) accompanies numerous neurological conditions, including migraine, stroke, and traumatic brain injury. There is significant interest in understanding the relationship between SD and neuronal injury. However, characteristics underlying SD and repolarization (RP) induced by global cerebral ischemia (e.g., cardiac arrest (CA)) and reperfusion are not well understood. Quantifying features of SD and RP during CA and cardiopulmonary resuscitation (CPR) may provide important metrics for diagnosis and prognosis of neurological injury from hypoxia-ischemia. We characterized SD and RP in a rodent model of asphyxial CA+CPR using a multimodal platform including electrocorticography (ECoG) and optical imaging. We detected SD and RP by (1) alternating current (AC), (2) direct current (DC), and (3) optical imaging of spreading ischemia, spreading edema, and vasoconstriction. Earlier SD (r=−0.80; p<0.001) and earlier RP (r=−0.71, p<0.001) were associated with better neurological recovery after 24hrs. SD+RP onset times predicted good vs poor neurological recovery with 82% sensitivity and 91% specificity. To our knowledge, this is the first preclinical study to link SD and RP characteristics with neurological recovery post-CA. These data suggest that SD and RP may be ultra-early, real-time prognostic markers of post-CA outcome, meriting further investigation into translational implications during global cerebral ischemia.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 30, 2019.
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Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model
Robert H. Wilson, Christian Crouzet, Donald E. Lee, Dishant P. Donga, Ayushi H. Patel, Afsheen Bazrafkan, Niki Maki, Masih A. Rafi, Maziar Moslehyazdi, Justin H. Pham, Mohammad Torabzadeh, Brooke E. Hjelm, Bruce J. Tromberg, Oswald Steward, Beth A. Lopour, Bernard Choi, Yama Akbari
bioRxiv 786210; doi: https://doi.org/10.1101/786210
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Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model
Robert H. Wilson, Christian Crouzet, Donald E. Lee, Dishant P. Donga, Ayushi H. Patel, Afsheen Bazrafkan, Niki Maki, Masih A. Rafi, Maziar Moslehyazdi, Justin H. Pham, Mohammad Torabzadeh, Brooke E. Hjelm, Bruce J. Tromberg, Oswald Steward, Beth A. Lopour, Bernard Choi, Yama Akbari
bioRxiv 786210; doi: https://doi.org/10.1101/786210

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