Research developments in the neurovascular unit and the blood‑brain barrier (Review)

Abstract

The neurovascular unit (NVU) is composed of neurons, glial cells, brain microvascular endothelial cells (BMECs), pericytes, and the extracellular matrix. The NVU controls the permeability of the blood-brain barrier (BBB) and protects the brain from harmful blood-borne and endogenous and exogenous substances. Among these, neurons transmit signals, astrocytes provide nutrients, microglia regulate inflammation, and BMECs and pericytes strengthen barrier tightness and coverage. These cells, due to their physical structure, anatomical location, or physiological function, maintain the microenvironment required for normal brain function. In this review, the BBB structure and mechanisms are examined to obtain a better understanding of the factors that influence BBB permeability. The findings may aid in safeguarding the BBB and provide potential therapeutic targets for drugs affecting the central nervous system.

Keywords: astrocyte; blood-brain barrier; brain microvascular endothelial cells; microglial; neurons; neurovascular unit; pericytes.

Figure 1

Composition of the neurovascular unit and the blood-brain barrier.

Figure 2

Molecular mechanism of neuronal apoptosis after brain injury. For example, after brain injury, SPAK is activated in neurons and phosphorylates downstream NKCC1. Sodium potassium chloride plasma and water enter neuronal cells, and the cells swell and rupture. This causes a pro-apoptotic effect. The TMEM2 membrane protein breaks down extracellular high-molecular-weight hyaluronic acid to low-molecular-weight hyaluronic acid and inhibits p38 and ERK signaling through CD44 entry into cells to exert brain protective effects. ACSL4 in the endoplasmic reticulum can convert 3-valent iron to 2-valent iron and activate the ROS system to accelerate cell apoptosis. PERK upregulates ATF4 to promote apoptosis by phosphorylating eIF2α. In addition, lysosomes promote neuronal apoptosis by secreting LRRK2 to phosphorylate RAB10. The arrows represent activation or upregulation, and the transverse lines represent inhibition. SPAK, STE20/SPS1-related proline/alanine-rich protein kinase; NKCC1, Na₊-K₊-Cl_- cotransporter 1; TMEM2, transmembrane protein 2; HMW-HA, high-molecular-weight hyaluronic acid; LMW-HA, low-molecular-weight hyaluronic acid; ACSL4, acyl-CoA synthetase long chain family member 4; ROS, reactive oxygen species; PERK, R-like endoplasmic reticulum kinase; ATF4, activating transcription factor 4; eIF2α, eukaryotic translation initiation factor 2α; LRRK2, leucine-rich repeat kinase 2; RAB10, Ras-related protein Rab-10; p, phosphorylated.