Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury

Neurobiology of Disease
Yi YangGary A Rosenberg

Abstract

Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage. MRI and IgG immunostaining showed regions with BBB damage, which corresponded with decreased endothelial TJPs, claudin-5, occludin, and ZO-1. Affected WM had increased expression of angiogenic factors, Ki67, NG2, VEGF-A, and MMP-3 in vascular endothelial cells and pericytes. To facilitate the study of angiogenesis, we treated rats with minocycline to block BBB disruption, reduce WM lesion size, and extend survival. Minocycline-treated rats showed increased VEGF-A protein, TJP formation, and oligodendrocyte proliferation. We propose that chronic hypoxia disrupts TJPs, increasing v...Continue Reading

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Citations

Dec 12, 2018·PloS One·Limor RazGary Rosenberg
Jan 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sha TanZhengqi Lu
Mar 14, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Chi GuGuohua Xi
Aug 2, 2019·Investigative Ophthalmology & Visual Science·Rebecca A BuchananGareth R Howell
Sep 23, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Laurel O SillerudYi Yang
Sep 16, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Patrick T Ronaldson, Thomas P Davis
Nov 18, 2018·Cell Transplantation·Jinwei PangYong Jiang
Jun 16, 2021·Nature Reviews. Nephrology·Zoltan UngvariAnna Csiszar
Jul 6, 2021·Frontiers in Cell and Developmental Biology·Hajime TakaseKen Arai
Jun 29, 2021·Frontiers in Neurology·Xiongjie FuGao Chen
Jul 3, 2021·International Journal of Molecular Sciences·Bojie XuXiangru Wang

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