Abstract

.There is a growing recognition regarding the importance of pial collateral flow in the protection from impending ischemic stroke both in preclinical and clinical studies. Collateral flow is also a major player in sensory stimulation-based protection from impending ischemic stroke. Doppler optical coherence tomography has been employed to image spatiotemporal patterns of collateral flow within the dorsal branches of the middle cerebral artery (MCA) as it provides a powerful tool for quantitative in vivo flow parameters imaging (velocity, flux, direction of flow, and radius of imaged branches). It was employed prior to and following dorsal permanent MCA occlusion (pMCAo) in rat models of treatment by protective sensory stimulation, untreated controls, or sham surgery controls. Unexpectedly, following pMCAo in the majority of subjects, some MCA branches continued to show anterograde blood flow patterns over time despite severing of the MCA. Further, in the presence of protective sensory stimulation, the anterograde velocity and flux were stronger and lasted longer than in retrograde flow branches, even within different branches of single subjects, but stimulated retrograde branches showed stronger flow parameters at 24 h. Our study suggests that the spatiotemporal patterns of collateral-based dorsal MCA flow are dynamic and provide a detailed description on the differential effects of protective sensory stimulation.

Highlights

  • Stroke is the fifth leading cause of death and the leading cause of long-term disability in the United States, with 88% of strokes originating from blood flow blockage known as ischemic strokes.[1]

  • Using a rat model of ischemic stroke achieved by dorsal permanent middle cerebral artery occlusion, we have repeatedly demonstrated that delivery of a whisker stimulation

  • The application of Doppler optical coherence tomography (DOCT) revealed several unexpected findings and insights regarding the spatiotemporal characteristics of the pial collateral-dorsal middle cerebral artery (MCA) system in our anesthetized rat permanent middle cerebral artery occlusion (pMCAo) model

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Summary

Introduction

Stroke is the fifth leading cause of death and the leading cause of long-term disability in the United States, with 88% of strokes originating from blood flow blockage known as ischemic strokes.[1]. Using a rat model of ischemic stroke achieved by dorsal permanent middle cerebral artery occlusion (pMCAo), we have repeatedly demonstrated that delivery of a whisker stimulation during a 2-h window following pMCAo directly evokes neuronal activity within the MCA ischemic territory. Such activation results in functional and structural protection from impending ischemic stroke, findings that were independently replicated in other labs.[5,6,7,8,9,10] Further, our findings[11,12,13,14,15,16,17,18] Our collateral-based findings further support and extend the emerging field known as “collateral therapeutics”—experimental stroke protection therapies

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