Changes in Cortical Microvasculature during Misery Perfusion Measured by Two-Photon Laser Scanning Microscopy

Abstract

This study aimed to examine the cortical microvessel diameter response to hypercapnia in misery perfusion using two-photon laser scanning microscopy (TPLSM). We evaluated whether the vascular response to hypercapnia could represent the cerebrovascular reserve. Cerebral blood flow (CBF) during normocapnia and hypercapnia was measured by laser-Doppler flowmetry through cranial windows in awake C57/BL6 mice before and at 1, 7, 14, and 28 days after unilateral common carotid artery occlusion (UCCAO). Diameters of the cortical microvessels during normocapnia and hypercapnia were also measured by TPLSM. Cerebral blood flow and the vascular response to hypercapnia were decreased after UCCAO. Before UCCAO, vasodilation during hypercapnia was found primarily in arterioles (22.9%±3.5%). At 14 days after UCCAO, arterioles, capillaries, and venules were autoregulatorily dilated by 79.5%±19.7%, 57.2%±32.3%, and 32.0%±10.8%, respectively. At the same time, the diameter response to hypercapnia in arterioles was significantly decreased to 1.9%±1.5%. A significant negative correlation was observed between autoregulatory vasodilation and the diameter response to hypercapnia in arterioles. Our findings indicate that arterioles play main roles in both autoregulatory vasodilation and hypercapnic vasodilation, and that the vascular response to hypercapnia can be used to estimate the cerebrovascular reserve.

Micro-Heterogeneity of Flow in a Mouse Model of Chronic Cerebral Hypoperfusion Revealed by Longitudinal Doppler Optical Coherence Tomography and Angiography

“…The venous dilation observed in this study after BCAS is in agreement with a recent longitudinal imaging study in awake, behaving mice after unilateral common carotid artery occlusion. 33 However, the slight initial arterial constriction relative to baseline (excluding collaterals) observed after BCAS in the present study contrasts with prominent arterial dilation relative to baseline observed after unilateral carotid artery occlusion in awake, behaving mice. 33 These differences are most likely because of anesthesia, but may also result, in part, from the larger degree of hypoperfusion in the BCAS model.…”

“…33 However, the slight initial arterial constriction relative to baseline (excluding collaterals) observed after BCAS in the present study contrasts with prominent arterial dilation relative to baseline observed after unilateral carotid artery occlusion in awake, behaving mice. 33 These differences are most likely because of anesthesia, but may also result, in part, from the larger degree of hypoperfusion in the BCAS model. Had this study been conducted in awake mice, we hypothesize that we would have observed arterial dilation similar to that observed in the carotid artery occlusion model.…”

“…Had this study been conducted in awake mice, we hypothesize that we would have observed arterial dilation similar to that observed in the carotid artery occlusion model. 33 Beyond investigation of the BCAS model, the extensive data set generated by this study also afforded several opportunities for methodological validation. Bilateral agreement of global cortical blood flow values (Figure 4) determined from arterioles suggested consistency of the Doppler OCT quantification method, even though vascular architecture differed greatly between hemispheres.…”

Vasodilation Mechanism of Cerebral Microvessels Induced by Neural Activation under High Baseline Cerebral Blood Flow Level Results from Hypercapnia in Awake Mice

“…The results were strongly in accord with the reports by Tajima et al . . Especially, the diameter change in arterioles during sensory stimulation showed a pronounced increase as compared with that of the condition of only CO 2 inhalation.…”

Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow

“…The chronic hypoperfusion model in mouse treated with unilateral common carotid occlusion in which the perfusion pressure is slightly below the autoregulation limit mimics one of the chronic perturbation states provoked in patients with persistent vasodilation and exhausted vasodilatory capacities (Tajima et al, 2014). The animal model that is chronically exposed to hypoxia is also considered as a stable method for induction of chronic perturbation, which evoke capillary remodeling, vasodilation, and reduced responses of the activity-induced dilation of penetrating arterioles, but not the pial arteries, resulting in the decrease in flow response to NVC (Masamoto et al, 2013aSekiguchi et al, 2014;Takuwa et al, 2013;Yoshihara et al, 2013).…”