Immune regulation in neurovascular units after traumatic brain injury

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Survivors may experience movement disorders, memory loss, and cognitive deficits. However, there is a lack of understanding of the pathophysiology of TBI-mediated neuroinflammation and neurodegeneration. The immune regulation process of TBI involves changes in the peripheral and central nervous system (CNS) immunity, and intracranial blood vessels are essential communication centers. The neurovascular unit (NVU) is responsible for coupling blood flow with brain activity, and comprises endothelial cells, pericytes, astrocyte end-feet, and vast regulatory nerve terminals. A stable NVU is the basis for normal brain function. The concept of the NVU emphasizes that cell-cell interactions between different types of cells are essential for maintaining brain homeostasis. Previous studies have explored the effects of immune system changes after TBI. The NVU can help us further understand the immune regulation process. Herein, we enumerate the paradoxes of primary immune activation and chronic immunosuppression. We describe the changes in immune cells, cytokines/chemokines, and neuroinflammation after TBI. The post-immunomodulatory changes in NVU components are discussed, and research exploring im-mune changes in the NVU pattern is also described. Finally, we summarize immune regulation therapies and drugs after TBI. Therapies and drugs that focus on immune regulation have shown great potential for neuro-protection. These findings will help us further understand the pathological processes after TBI.

Automated summary

Traumatic brain injury (TBI) is a leading cause of death and disability globally, and survivors often face movement disorders, memory loss, and cognitive impairments. However, the understanding of the underlying pathophysiology of TBI-induced neuroinflammation and neurodegeneration remains limited. Changes in peripheral and central nervous system immunity, as well as alterations in the neurovascular unit (NVU), play crucial roles in the immune regulation process. The NVU, consisting of different cell types, is responsible for maintaining brain homeostasis, and investigating immune changes in the NVU pattern can provide valuable insights into post-TBI pathological processes.