T-Lymphocyte Interactions with the Neurovascular Unit: Implications in Intracerebral Hemorrhage

Abstract

In the pathophysiology of hemorrhagic stroke, the perturbation of the neurovascular unit (NVU), a functional group of the microvascular and brain intrinsic cellular components, is implicated in the progression of secondary injury and partially informs the ultimate patient outcome. Given the broad NVU functions in maintaining healthy brain homeostasis through its maintenance of nutrients and energy substrates, partitioning central and peripheral immune components, and expulsion of protein and metabolic waste, intracerebral hemorrhage (ICH)-induced dysregulation of the NVU directly contributes to numerous destructive processes in the post-stroke sequelae. In ICH, the damaged NVU precipitates the emergence and evolution of perihematomal edema as well as the breakdown of the blood–brain barrier structural coherence and function, which are critical facets during secondary ICH injury. As a gateway to the central nervous system, the NVU is among the first components to interact with the peripheral immune cells mobilized toward the injured brain. The release of signaling molecules and direct cellular contact between NVU cells and infiltrating leukocytes is a factor in the dysregulation of NVU functions and further adds to the acute neuroinflammatory environment of the ICH brain. Thus, the interactions between the NVU and immune cells, and their reverberating consequences, are an area of increasing research interest for understanding the complex pathophysiology of post-stroke injury. This review focuses on the interactions of T-lymphocytes, a major cell of the adaptive immunity with expansive effector function, with the NVU in the context of ICH. In cataloging the relevant clinical and experimental studies highlighting the synergistic actions of T-lymphocytes and the NVU in ICH injury, this review aimed to feature emergent knowledge of T cells in the hemorrhagic brain and their diverse involvement with the neurovascular unit in this disease.

The immunomodulatory mechanism of acupuncture treatment for ischemic stroke: research progress, prospects, and future direction

“…The acute and chronic phases of IS and the long-term effects of stroke are greatly affected by the immune system ( 10 ). The immune response after IS involves innate and adaptive immunity in the central and peripheral nervous systems ( 11 ). Targeting regulatory immunity is a promising approach for reducing stroke-related dysfunction.…”

The challenge of managing ischemic stroke in brucellosis: a case report

“…Nevertheless, there have been a few reported cases of brucellosis complicated by HS. Previous studies indicate the involvement of infiltrating T lymphocytes in the pathophysiological process of cerebral hemorrhage ( 12 ). However, the precise mechanism by which brucellosis contributes to the occurrence and progression of stroke requires further investigation.…”

MicroRNAs modulate neuroinflammation after intracerebral hemorrhage: Prospects for new therapy

“…Studies have found that T cells can patrol the cerebrospinal fluid in the healthy CNS to conduct immune surveillance ( 107 ). And after ICH, activated T cells can cross the BBB and contribute to brain injury through a number of mechanisms such as microvascular dysfunction, neuronal apoptosis, inflammatory molecules production, neutrophil recruitment, and interaction with microglia ( 108 ). The major subtypes of T cells include CD4+ Th cells (including Th1, Th2, and Th17 cells), CD8+ cytotoxic T cells, memory T cells, and T-regulatory (Treg) cells.…”

“…They have different molecular expression profiles and cellular functions, with some mainly exerting injurious effects and others being reparative after ICH. Among them, CD4+ T cells are the predominant populations in the post-ICH brain milieu ( 108 ). Studies suggest that many miRNAs can serve as positive or negative regulators of T cell development and function, exemplified by the fact that models with certain miRNA deficiency can have CD4+ and CD8+ T cell dysfunction ( 109 ).…”