Engineering Neurovascular Unit and Blood–Brain Barrier for Ischemic Stroke Modeling

Abstract

Ischemic stroke is a primary vascular disease of the central nervous system characterized by high morbidity, mortality, and healthcare costs. As conventional ischemic stroke models fail to predict therapeutic efficacy, in vitro neurovascular unit (NVU)/blood–brain barrier (BBB) models are utilized to model ischemic stroke through replicating the cell–cell interactions and mimicking the blood flow and anatomical features of the brain. Here, an overview of transwell, microfluidic, and hydrogel‐based NVU/BBB models is provided, including cell types, engineering approaches, and the simulation of physiological and pathological features of NVU/BBB after ischemic stroke. Collectively, recent advances in 3D‐printed NVU models are emphasized, which are anticipated to be a promising system for more reliable mechanistic studies and preclinical drug screenings that can eventually accelerate the drug development process for the ischemic stroke therapy.

Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood–Brain Barrier

“…As discussed above, the interaction between brain tissue and blood circulation actually takes place on the neurovascular units (NVUs), structures that include different cell types, and their associated extracellular matrix (ECM). In order to create NVU-like structures, pluripotent stem cells (iPSCs) can be induced to differentiate in the NVU cell types and then cultured together in an ECM-like environment [163][164][165]. A similar model, comprising neural and endothelial cells from newborn rats capable of self-assembly in a 3D structure that included a Matrigel ECM, was found to present vascular and BBB-like structures.…”

“…These models have been utilized in the case of ischemic stroke, trying to recreate the cell interactions and the circulatory flow typical of the brain neurovascular units (NVUs) [165].…”

Deciphering Post-Stroke Sleep Disorders: Unveiling Neurological Mechanisms in the Realm of Brain Science

“…Surrounding the cerebral blood vessels are various cell types, emitting substances into the extracellular domain and adjacent to blood vessels, orchestrating cerebral blood flow. These cell types, encompassing endothelial cells, pericytes, astrocytes, perivascular macrophages and peripheral microglia, are collectively termed neurovascular units (NVUs) [80,81] (Figure 2). NVU meticulously orchestrates the regulation of the blood-brain barrier, CBF, blood flow velocity and regional cerebral blood volume, ensuring the stability of the brain's microenvironment [82][83][84][85][86].…”