Crosstalk between Inflammation and the BBB in Stroke

Abstract

: The blood-brain barrier (BBB), which is located at the interface between the central nervous system (CNS) and the circulatory system, is instrumental in establishing and maintaining the microenvironmental homeostasis of the CNS. BBB disruption following stroke promotes inflammation by enabling leukocytes, T cells and other immune cells to migrate via both the paracellular and transcellular routes across the BBB and to infiltrate the CNS parenchyma. Leukocytes promote the removal of necrotic tissues and neuronal recovery, but they also aggravate BBB injury and exacerbate stroke outcomes, especially after late reperfusion. Moreover, the swelling of astrocyte endfeet is thought to contribute to the ‘no-reflow’ phenomenon observed after cerebral ischemia, that is, blood flow cannot return to capillaries after recanalization of large blood vessels. Pericyte recruitment and subsequent coverage of endothelial cells (ECs) alleviates BBB disruption, which causes the transmigration of inflammatory cells across the BBB to be a dynamic process. Furthermore, interneurons and perivascular microglia also make contacts with ECs, astrocytes and pericytes to establish the neurovascular unit. BBB-derived factors after cerebral ischemia triggered microglial activation. During the later stage of injury, microglia remain associated with brain ECs and contribute to repair mechanisms, including postinjury angiogenesis, by acquiring a protective phenotype, which possibly occurs through the release of microglia-derived soluble factors. Taken together, we reviewed how dynamic and bidirectional crosstalk between inflammation and the BBB during stroke and revealed targeted interventions based on crosstalk between inflammation and the BBB, which will provide novel insights for developing new therapeutic strategies.

Inhibition of the NKCC1/NF-κB Signaling Pathway Decreases Inflammation and Improves Brain Edema and Nerve Cell Apoptosis in an SBI Rat Model

“…Under normal physiological conditions of brain tissue, microglia cells are dormant. After brain injury, microglia are activated and release inflammatory cytokines IL-1β, IL-6, and TNF-α (Huang et al, 2020b). This allows inflammatory substances to leak into the brain parenchyma, causing widespread neuroinflammation, leading to brain edema, and impaired nerve function (Haruwaka et al, 2019).…”

The correlation between novel peripheral blood cell ratios and 90-day mortality in patients with acute ischemic stroke

“…Ischemic stroke can cause immune disorders and induce systemic inflammatory reactions characterized by changes in peripheral leukocytes [15]. In turn, activated leukocytes can aggravate neuronal damage and expand infarct sizes through various pathophysiological pathways [16,17]. Previous studies [18,19] proved that there was a significant correlation between stroke severity and peripheral leukocyte count.…”

Resolvin D1 ameliorates Inflammation-Mediated Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in rats by Modulating A20 and NLRP3 Inflammasome

“…An excessive inflammatory response disrupts the junctional complex in the BBB, leading to BBB dysfunction in several inflammatory CNS diseases, including trauma, Alzheimer's disease, and SAH (Chen et al, 2014;Bennett et al, 2020;Kim et al, 2020). The destroyed BBB allows peripheral neutrophils and other immune cells to infiltrate the CNS (Huang et al, 2020). Additionally, studies have confirmed that activated microglia and recruited neutrophils release various pro-inflammatory factors and exacerbate the inflammatory response after SAH (Ye et al, 2018;Tao et al, 2019).…”