Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?

Abstract

Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation of immune cells plays a critical role in BBB disruption after ischemic stroke. Infiltrating blood-borne immune cells (neutrophils, monocytes, and T lymphocytes) increase BBB permeability, as they cause microvascular disorder and secrete inflammation-associated molecules. In contrast, they promote BBB repair and angiogenesis in the latter phase of ischemic stroke. The profound immunological effects of cerebral immune cells (microglia, astrocytes, and pericytes) on BBB disruption have been underestimated in ischemic stroke. Post-stroke microglia and astrocytes can adopt both an M1/A1 or M2/A2 phenotype, which influence BBB integrity differently. However, whether pericytes acquire microglia phenotype and exert immunological effects on the BBB remains controversial. Thus, better understanding the inflammatory mechanism underlying BBB disruption can lead to the identification of more promising biological targets to develop treatments that minimize the onset of life-threatening complications and to improve existing treatments in patients. However, early attempts to inhibit the infiltration of circulating immune cells into the brain by blocking adhesion molecules, that were successful in experimental stroke failed in clinical trials. Therefore, new immunoregulatory therapeutic strategies for acute ischemic stroke are desperately warranted. Herein, we highlight the role of circulating and cerebral immune cells in BBB disruption and the crosstalk between them following acute ischemic stroke. Using a robust theoretical background, we discuss potential and effective immunotherapeutic targets to regulate BBB permeability after acute ischemic stroke.

Leukocyte-derived ratios are associated with late-life any type dementia: a cross-sectional analysis of the Mugello study

“…In previous studies, LMR was reported to be a marker of clinical progression [24], disease complications and poor outcome [25] in acute ischemic and hemorrhagic stroke, but not in the chronic phase of the disease. The temporal trend of immune cells infiltrating the brain, and their peripheral variations have been recently reviewed [26], even if studied mostly in animal models. Neutrophils, monocytes, and lymphocytes increased in the ischemic hemisphere in just a few hours, and could be found locally for 15-30 days after the ischemic event.…”

Molecular Mechanisms of Neuroimmune Crosstalk in the Pathogenesis of Stroke

“…The immediate effects of ischemic injury are induced by the reduction of cerebral blood flow, oxygen, and nutrients, leading to cell death via necrosis and apoptosis in the ischemic core region. During this process, danger-associated molecular patterns (DAMPs), which include high mobility group box-1 (HMGB1) and peroxiredoxin family proteins, are released to activate brain resident microglial cells by pattern recognition receptors (PRRs), including toll-like receptors (TLRs) and initiate leukocyte transmigration, by secreting interleukin (IL)-1, IL-6, matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)α [30,[37][38][39][40][41]. In the periphery of the ischemic core, called the penumbra, neurons may survive and provoke pathogenic factors, including calcium overload, oxidative stress, and glutamate excitotoxicity, that can cause more cell death [30].…”

Identification of Hub Genes Associated with Immune Infiltration in Cardioembolic Stroke by Whole Blood Transcriptome Analysis

“…Stroke is a devastating cerebrovascular disease, containing two types: ischemic stroke (IS) and hemorrhagic stroke (HS). Accounting for approximately 80% of all cases, ischemic stroke is the most common subtype, which is triggered by arterial embolization or thromboembolism in the cerebrum [ 1 ]. A wide range of clinical manifestations of IS includes physical disability, impaired cognitive and emotional abilities [ 2 ].…”