Neurovascular dynamics of repeated cortical spreading depolarizations after acute brain injury
Hanzhi T. Zhao,
Mary Claire Tuohy,
Daniel Chow,
Mariel G. Kozberg,
Sharon H. Kim,
Mohammed A. Shaik,
Elizabeth M.C. Hillman
Affiliations
Hanzhi T. Zhao
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA
Mary Claire Tuohy
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA
Daniel Chow
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA
Mariel G. Kozberg
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA
Sharon H. Kim
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA
Mohammed A. Shaik
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA
Elizabeth M.C. Hillman
Laboratory for Functional Optical Imaging, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA; Corresponding author
Summary: Cortical spreading depolarizations (CSDs) are increasingly suspected to play an exacerbating role in a range of acute brain injuries, including stroke, possibly through their interactions with cortical blood flow. We use simultaneous wide-field imaging of neural activity and hemodynamics in Thy1-GCaMP6f mice to explore the neurovascular dynamics of CSDs during and following Rose Bengal-mediated photothrombosis. CSDs are observed in all mice as slow-moving waves of GCaMP fluorescence extending far beyond the photothrombotic area. Initial CSDs are accompanied by profound vasoconstriction and leave residual oligemia and ischemia in their wake. Later, CSDs evoke variable responses, from constriction to biphasic to vasodilation. However, CSD-evoked vasoconstriction is found to be more likely during rapid, high-amplitude CSDs in regions with stronger oligemia and ischemia, which, in turn, worsens after each repeated CSD. This feedback loop may explain the variable but potentially devastating effects of CSDs in the context of acute brain injury.
