Imaging the time course, morphology, neuronal tissue compression, and resolution of cerebral microhemorrhages in mice using intravital two-photon microscopy: insights into arteriolar, capillary, and venular origin

• Published in: GeroScience 2023-10, Vol.45 (5), p.2851-2872
• Main Authors: Faakye, Janet, Nyúl-Tóth, Ádám, Gulej, Rafal, Csik, Boglarka, Tarantini, Stefano, Shanmugarama, Santny, Prodan, Calin, Mukli, Peter, Yabluchanskiy, Andriy, Conley, Shannon, Toth, Peter, Csiszar, Anna, Ungvari, Zoltan
• Format: Article
• Language: English
• Subjects: Aging; Animals; Arterioles; Arterioles - diagnostic imaging; Biomedical and Life Sciences; Capillaries; Capillaries - diagnostic imaging; Cell Biology; Cerebral Hemorrhage - etiology; Cerebral Small Vessel Diseases - complications; Cerebral Small Vessel Diseases - diagnostic imaging; Cognitive ability; Dementia; Dementia - complications; Dementia disorders; Extravasation; Geriatrics/Gerontology; Gliosis; Ischemia; Life Sciences; Light effects; Mice; Microscopy; Molecular Medicine; Morphology; Older people; Original; Original Article; Pathogenesis; Vascular diseases; Venules
• ISSN: 2509-2723; 2509-2715; 2509-2723
• DOI: 10.1007/s11357-023-00839-w

Cerebral microhemorrhages (CMHs, microbleeds), a manifestation of age-related cerebral small vessel disease, contribute to the pathogenesis of cognitive decline and dementia in older adults. Histological studies have revealed that CMHs exhibit distinct morphologies, which may be attributed to differences in intravascular pressure and the size of the vessels of origin. Our study aimed to establish a direct relationship between the size/morphology of CMHs and the size/anatomy of the microvessel of origin. To achieve this goal, we adapted and optimized intravital two-photon microscopy-based imaging methods to monitor the development of CMHs in mice equipped with a chronic cranial window upon high-energy laser light-induced photodisruption of a targeted cortical arteriole, capillary, or venule. We assessed the time course of extravasation of fluorescently labeled blood and determined the morphology and size/volume of the induced CMHs. Our findings reveal striking similarities between the bleed morphologies observed in hypertension-induced CMHs in models of aging and those originating from different targeted vessels via multiphoton laser ablation. Arteriolar bleeds, which are larger (> 100 μm) and more widely dispersed, are distinguished from venular bleeds, which are smaller and exhibit a distinct diffuse morphology. Capillary bleeds are circular and smaller (