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      Longitudinal optical coherence tomography imaging of tissue repair and microvasculature regeneration and function after targeted cerebral ischemia

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          Abstract.

          Significance: Understanding how the brain recovers from cerebral tissue and vascular damage after an ischemic event can help develop new therapeutic strategies for the treatment of stroke.

          Aim: We investigated cerebral tissue repair and microvasculature regeneration and function after a targeted ischemic stroke.

          Approach: Following photothrombosis occlusion of microvasculature, chronic optical coherence tomography (OCT)-based angiography was used to track ischemic tissue repair and microvasculature regeneration at three different cortical depths and up to 28 days in awake animals. Capillary network orientation analysis was performed to study the structural pattern of newly formed microvasculature. Based on the time-resolved OCT-angiography, we also investigated capillary stalling, which is likely related to ischemic stroke-induced inflammation.

          Results: Deeper cerebral tissue was found to have a larger ischemic area than shallower regions at any time point during the course of poststroke recovery, which suggests that cerebral tissue located deep in the cortex is more vulnerable. Regenerated microvasculature had a highly organized pattern at all cortical depths with a higher degree of structural reorganization in deeper regions. Additionally, capillary stalling event analysis revealed that cerebral ischemia augmented stalling events considerably.

          Conclusion: Longitudinal OCT angiography reveals that regenerated capillary network has a highly directional pattern and an increased density and incidence of capillary stalling event.

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          Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy.

          R Rezakhaniha, A Agianniotis, J T C Schrauwen … (2012)
          Mechanical properties of the adventitia are largely determined by the organization of collagen fibers. Measurements on the waviness and orientation of collagen, particularly at the zero-stress state, are necessary to relate the structural organization of collagen to the mechanical response of the adventitia. Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid arteries ex vivo. The arteries were cut open along their longitudinal axes to get the zero-stress state. We used semi-manual and automatic techniques to measure parameters related to the waviness and orientation of fibers. Our results showed that the straightness parameter (defined as the ratio between the distances of endpoints of a fiber to its length) was distributed with a beta distribution (mean value 0.72, variance 0.028) and did not depend on the mean angle orientation of fibers. Local angular density distributions revealed four axially symmetric families of fibers with mean directions of 0°, 90°, 43° and -43°, with respect to the axial direction of the artery, and corresponding circular standard deviations of 40°, 47°, 37° and 37°. The distribution of local orientations was shifted to the circumferential direction when measured in arteries at the zero-load state (intact), as compared to arteries at the zero-stress state (cut-open). Information on collagen fiber waviness and orientation, such as obtained in this study, could be used to develop structural models of the adventitia, providing better means for analyzing and understanding the mechanical properties of vascular wall.
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            Targeting neutrophils in ischemic stroke: translational insights from experimental studies.

            Glen Jickling, DaZhi Liu, Bradley Ander … (2015)
            Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood-brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions.
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              Induction of reproducible brain infarction by photochemically initiated thrombosis.

              B D Watson, W Dietrich, R Busto … (1985)
              We have used a photochemical reaction in vivo to induce reproducible thrombosis leading to cerebral infarction in rats. After the intravenous injection of rose bengal, a potent photosensitizing dye, an ischemic lesion was formed by irradiating the left parietal convexity of the exposed skull for 20 minutes with green light (560 nm) from a filtered xenon arc lamp. Animals were allowed to survive from 30 minutes to 15 days after irradiation. Early microscopic alterations within the irradiated zone included the formation of thrombotic plugs and adjacent red blood cell stasis within pial and parenchymal vessels. Scanning electron microscopy revealed frequent platelet aggregates adhering to the vascular endothelium, often resulting in vascular occlusion. Carbon-black brain perfusion demonstrated that occlusion of vascular channels progressed after irradiation and was complete within 4 hours. Histopathological examination at 1, 5, and 15 days revealed that the associated infarct evolved reproducibly through several characteristic stages, including a phase of massive macrophage infiltration. Although cerebral infarction in this model is initiated by thrombosis of small blood vessels, the fact that the main pathological features of stroke are consistently reproduced should permit its use in assessing treatment regimens. Further, the capability of producing infarction in preselected cortical regions may facilitate the study of behavioral, functional, and structural consequences of acute and chronic stroke.
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                Author and article information

                Contributors
                Yuankang Lu
                Xuecong Lu
                Cong Zhang:
                ORCID: https://orcid.org/0000-0002-4026-2668
                Paul J. Marchand
                Frédéric Lesage:
                ORCID: https://orcid.org/0000-0003-3699-1283
                Journal
                Journal ID (nlm-ta): J Biomed Opt
                Journal ID (iso-abbrev): J Biomed Opt
                Journal ID (coden): JBOPFO
                Journal ID (publisher-id): JBO
                Title: Journal of Biomedical Optics
                Publisher: Society of Photo-Optical Instrumentation Engineers
                ISSN (Print): 1083-3668
                ISSN (Electronic): 1560-2281
                Publication date (Electronic): 13 April 2020
                Publication date (Print): April 2020
                Publication date PMC-release: 13 April 2020
                Volume: 25
                Issue: 4
                Electronic Location Identifier: 046002
                Affiliations
                [a ]Laboratoire d’Imagerie Optique et Moléculaire , École Polytechnique de Montréal, Montréal, Québec, Canada
                [b ]Université de Montreal , Montréal, Québec, Canada
                [c ]Institut de Cardiologie de Montréal , Montréal, Québec, Canada
                Author notes
                [* ]Address all correspondence to Frédéric Lesage, E-mail: frederic.lesage@ 123456polymtl.ca
                Author information
                https://orcid.org/0000-0002-4026-2668
                https://orcid.org/0000-0003-3699-1283
                Article
                Publisher-manuscript ID: JBO-190342R Publisher ID: 190342R
                DOI: 10.1117/1.JBO.25.4.046002
                PMC ID: 7152803
                PubMed ID: 32285652
                SO-VID: 7a7df6b7-deb8-405a-b323-eeeb06c82084
                Copyright © © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
                History
                Date received : 25 September 2019
                Date accepted : 9 March 2020
                Page count
                Figures: 7, Tables: 0, References: 42, Pages: 15
                Funding
                Funded by: Canadian Institutes of Health Research https://doi.org/10.13039/501100000024
                Award ID: 299166
                Funded by: Natural Sciences and Engineering Research Council of Canada https://doi.org/10.13039/501100000038
                Award ID: 239876-2011
                Funded by: TransMedTech Institute
                Funded by: Swiss National Science Foundation
                Categories
                Subject: Imaging
                Subject: Paper
                Custom metadata
                running-head Lu et al.: Longitudinal optical coherence tomography imaging of tissue repair and microvasculature…

                ScienceOpen disciplines: Biomedical engineering
                Keywords: optical coherence tomography-angiography,photothrombosis,microvasculature,capillary stalling
                Data availability:
                ScienceOpen disciplines: Biomedical engineering
                Keywords: optical coherence tomography-angiography, photothrombosis, microvasculature, capillary stalling

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