Abstract

Occlusions of bilateral common carotid arteries (bi-CCA) in mice are popular models for the investigation of transient forebrain ischemia. Currently available technologies for assessing cerebral blood flow (CBF) and oxygenation in ischemic mice have limitations. This study tests a novel near-infrared diffuse correlation spectroscopy (DCS) flow-oximeter for monitoring both CBF and cerebral oxygenation in mice undergoing repeated transient forebrain ischemia. Concurrent flow measurements in a mouse brain were first conducted for validation purposes; DCS measurement was found highly correlated with laser Doppler measurement (R2 = 0.94) and less susceptible to motion artifacts. With unique designs in experimental protocols and fiber-optic probes, we have demonstrated high sensitivities of DCS flow-oximeter in detecting the regional heterogeneity of CBF responses in different hemispheres and global changes of both CBF and cerebral oxygenation across two hemispheres in mice undergoing repeated 2-minute bi-CCA occlusions over 5 days. More than 75% CBF reductions were found during bi-CCA occlusions in mice, which may be considered as a threshold to determine a successful bi-CCA occlusion. With the progress of repeated 2-minute bi-CCA occlusions over days, a longitudinal decline in the magnitudes of CBF reduction was observed, indicating the brain adaptation to cerebral ischemia through the repeated preconditioning.

Highlights

  • Stroke is the third cause of death in US with over 700,000 occurrences, 200,000 deaths and more disabilities annually [1]

  • The short-term less-injurious interruptions (e.g., 2 minutes) of cerebral blood flow (CBF) enable the neurons to obtain the protection against the subsequently long episode of ischemia and enhance the cerebral ischemic tolerance, which is known as cerebral ischemic preconditioning [1, 2, 4, 6, 7]

  • Note that the laser Doppler flowmetry (LDF) measurement is sensitive to motions, which can be seen from the motion artifacts in the top panel of Fig. 3a

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Summary

Introduction

Stroke is the third cause of death in US with over 700,000 occurrences, 200,000 deaths and more disabilities annually [1]. Animal models of cerebral ischemia contribute greatly to the understanding of stroke pathophysiology [3]. The duration and frequency of cerebral ischemia and the interval between occurrences can significantly affect neuronal viability and vascular response, resulting in different pathophysiological consequences [1, 2, 6]. The short-term less-injurious interruptions (e.g., 2 minutes) of cerebral blood flow (CBF) enable the neurons to obtain the protection against the subsequently long episode of ischemia and enhance the cerebral ischemic tolerance, which is known as cerebral ischemic preconditioning [1, 2, 4, 6, 7]. Preconditioning may reduce the thereafter ischemia-reperfusion (I-R) injury [1]. The medium-term cerebral ischemia (e.g., 10 minutes) could induce transient ischemic

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