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Review
. 2023 Sep 28:14:1248970.
doi: 10.3389/fneur.2023.1248970. eCollection 2023.

Stroke-induced damage on the blood-brain barrier

Song Xue  1 , Xin Zhou  1 , Zhi-Hui Yang  1 , Xiang-Kun Si  1 , Xin Sun  1
Affiliations
Review

Stroke-induced damage on the blood-brain barrier

Song Xue et al. Front Neurol. .

Abstract

The blood-brain barrier (BBB) is a functional phenotype exhibited by the neurovascular unit (NVU). It is maintained and regulated by the interaction between cellular and non-cellular matrix components of the NVU. The BBB plays a vital role in maintaining the dynamic stability of the intracerebral microenvironment as a barrier layer at the critical interface between the blood and neural tissues. The large contact area (approximately 20 m2/1.3 kg brain) and short diffusion distance between neurons and capillaries allow endothelial cells to dominate the regulatory role. The NVU is a structural component of the BBB. Individual cells and components of the NVU work together to maintain BBB stability. One of the hallmarks of acute ischemic stroke is the disruption of the BBB, including impaired function of the tight junction and other molecules, as well as increased BBB permeability, leading to brain edema and a range of clinical symptoms. This review summarizes the cellular composition of the BBB and describes the protein composition of the barrier functional junction complex and the mechanisms regulating acute ischemic stroke-induced BBB disruption.

Keywords: astrocytes; blood–brain barrier; ischemic stroke; microvascular endothelial cells; neurovascular unit.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of NVU. Microvessels adjacent to highly vascularized brain tissues provide blood flow to the surrounding nerve cells. Brain microvascular endothelial cells, pericytes, astrocytes, basement membrane, neurons, and microglia form the neurovascular unit.
Figure 2
Figure 2
Molecular composition of BBB tight junctions and major changes in acute ischemic stroke. The TJ consists of three integral membrane proteins, claudins, occludin, and junction adhesion molecules (JAMs), and a number of cytoplasmic accessory proteins including zonula occludens 1, 2, and 3 (ZO-1, 2, 3), cingulin, afadin-6 (AF-6), and 7H6. Membrane proteins are connected to actin by cytoplasmic proteins. The carboxy-terminal serine residues of occludin are linked to the cytoskeleton via ZO-1 and ZO-2. Adherens junctions are formed by cadherins, catenins, vinculin, and actinin. Among the important molecules are vascular endothelial cadherin (VE-cadherin) and platelet endothelial cell adhesion molecules (PECAM). The figure shows the changes in blood-brain barrier permeability at different times after the onset of ischemic stroke, as well as the main pathophysiological processes in each stage. Acutely elevated local cerebral blood flow can lead to initial reperfusion permeability. The opening of the BBB presents a biphasic phenomenon. The first phase usually occurs within 6 h after an acute cerebral infarction. The second phase usually occurs within 72 h after the onset of an acute cerebral infarction. Elevated Ca2+ concentration in the endothelial under ischemic hypoxic conditions regulates TJ proteins' stability through multiple pathways. PKC α can act on VE-cadherin to participate in AJ degradation. PKC βII and PKC γ cause TJ changes by regulating NO activity. Src phosphorylates occludin and ZO-1. Elevated MMP-9 reduces ZO-1 expression and its cytoplasmic translocation, leading to barrier disruption.
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Grants and funding

This project was supported by the Science and Technology Department of Jilin Province (YDZJ202301ZYTS520) to XS.

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