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Shih, A. Y.

Publications and source records attributed to Shih, A. Y..

2 recordsLinked to original sources

Classification of brain pericytes based on cell structure, location, and α-smooth muscle actin content

Smooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with mixed phenotype of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and -smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3-D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of -smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.

neuroscience

Spontaneous development of cerebrovascular pathology and microinfarcts in a mouse model of sickle cell disease.

Stroke is a dramatic complication of sickle cell disease (SCD) and is associated with aneurysms, moya moya, intravascular thrombi, cerebral hyperemia and increased vessel tortuosity. We show that aged SCD mice spontaneously develop the characteristics features of cerebral vasculopathy seen in human SCD. Thirteen month old Townes SCD mice and age-matched controls had a cranial windows implanted over the somatosensory cortex. Cortical capillaries were imaged using in vivo two-photon microscopy after the blood plasma was labeled with a fluorescent dye. Results showed that SCD mice compared to controls, had significantly higher red blood cell (RBC) velocity and capillary vessel diameter. SCD mice also had a significantly higher number of occlusive events in the capillary bed, resulting in more stalling of RBC flow. Microvascular topology was also altered, as SCD mice had significantly higher vessel tortuosity and shorter capillary branch lengths. Finally, post-mortem analyses revealed a greater number of cortical microinfarcts, likely caused by vascular occlusion since local tissue hypoxia and blood-brain barrier leakage was prominent. We concluded that aged Townes sickle cell mice spontaneously develop SCD-associated cerebral vasculopathy, and that in vivo two-photon imaging is a powerful approach to investigate the mechanisms of vascular complications in SCD.

neuroscience