Need for a Paradigm Shift in the Treatment of Ischemic Stroke: The Blood-Brain Barrier

Alonso-Alonso ML, Sampedro-Viana A, Fernández-Rodicio S, Bazarra-Barreiros M, Ouro A, Sobrino T, Campos F, Castillo J, Hervella P, Iglesias-Rey R. Int J Mol Sci. 2022 Aug 22;23(16):9486. doi: 10.3390/ijms23169486. PMID: 36012745

Abstract: Blood-brain barrier (BBB) integrity is essential to maintaining brain health. Aging-related alterations could lead to chronic progressive leakiness of the BBB, which is directly correlated with cerebrovascular diseases. Indeed, the BBB breakdown during acute ischemic stroke is critical. Itremains unclear, however, whether BBB dysfunction is one of the first events that leads to brain disease or a down-stream consequence. This review will focus on the BBB dysfunction associated with cerebrovascular disease. An added difficulty is its association with the deleterious or reparative effect, which depends on the stroke phase. We will first outline the BBB structure and function. Then, we will focus on the spatiotemporal chronic, slow, and progressive BBB alteration related to ischemic stroke. Finally, we will propose a new perspective on preventive therapeutic strategies associated with brain aging based on targeting specific components of the BBB. Understanding BBB age-evolutions will be beneficial for new drug development and the identification of the best performance window times. This could have a direct impact on clinical translation and personalised medicine.

This research was funded by Spanish Ministry of Science and Innovation (SAF2017-84267-R, RTI2018-102165-B-I00, RTC2019-007373-1), PDC2021-121455-I00, Xunta de Galicia (Consellería de Educación: IN607A2018/3, IN607D2020/09), Instituto de Salud Carlos III (ISCIII) (PI17/00540, PI17/01103), ISCIII/PI21/01256/Co-financed by the European Union, Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019/0001), RICORS-ICTUS (Cerebrovascular diseases) D21/0006/0003. T. Sobrino (CPII17/00027), and F. Campos (CPII19/00020) from the Miguel Servet Program of Instituto de Salud Carlos III.