Effects of renovascular hypertension and physical training on permeability and on ultrastructural changes in the blood-brain barrier.

• Grant number: 22/14337-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lisete Compagno Michelini
• Grantee: Sany Martins Pérego
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/14544-6 - Blood-brain barrier: a new paradigm in the treatment of hypertension, AP.TEM
• Associated scholarship(s): 24/21699-7 - UNDERSTANDING THE EFFECT OF RENOVASCULAR HYPERTENSION ON GLIAL CELLS, BE.EP.DR

Abstract

After proving that chronic hypertension was associated with dysfunction of the blood-brain barrier (BBB) and promoting deficits of autonomic control in important areas for the autonomic balance (BIANCARDI et al, 2014), our group demonstrated that both dysfunctions were reversed by aerobic training (BUTTLER et al, 2017). Recent researchs from our laboratory also observed that both the elevation of pressure levels and the BBB extravasation index were corrected by training and accompanied by increase of transcytotic vesicle formation and less expression of caveolin-1 (one of the main components of vesicles wich is responsible for transcellular transport) in BBB endothelial cells, but did not affect tight junctions (CÂNDIDO & MICHELINI, article in publication; FRAGAS et al, 2021), suggesting transcytosis as one of the key mechanisms to trigger alterations. However, there is still no information about the effects of hypertension and aerobic training on podocyte morphology/functionality of astrocytes that externally coat and isolate the BBB in areas of autonomic control. We also do not know whether the structural/functional changes that the BBB undergoes in the face of hypertension and aerobic training are specific to primary hypertension (the studies listed above were always conducted in SHR) or more generic characterizing other models of chronic hypertension such as secondary hypertension. Until now, it is our working hypothesis that hypertension and aerobic training may modificate BBB permeability in secondary hypertension model in a similar way to that observed in SHR model. As well we want to understand if structural/functional alterations of astrocyte podocytes may, somehow, contribuite to impairment of BBB functionality in hypertension or contribute itself to its correction after aerobic training.