High-Mobility Group Box 1 in Spinal Cord Injury and Its Potential Role in Brain Functional Remodeling After Spinal Cord Injury.

High-mobility group box 1 (HMGB1) is a nonhistone nuclear protein, the functions of which depend on its subcellular location. It is actively or passively secreted into the blood and/or cerebrospinal fluid (CSF) and can be used as a prognostic indicator of disease. HMGB1 released into the bloodstream can cause pathological reactions in distant organs, and entry into the CSF can destroy the blood-brain barrier and aggravate brain injuries. HMGB1 expression has been reported to be increased in the tissues of spinal cord injury (SCI) patients and involved in the regulation of neuroinflammation, neuronal apoptosis, and ferroptosis. SCI can lead to brain changes, resulting in neuropathic pain, depression, and cognitive dysfunction, but the specific mechanism is unknown. It remains unclear whether HMGB1 plays an important role in brain functional remodeling after SCI. Damaged cells at the site of SCI passively release HMGB1, which travels to the brain via the blood, CSF, and/or axonal transport, destroys the blood-brain barrier, and causes pathological changes in the brain. This may explain the remodeling of brain function that occurs after SCI. In this minireview, we introduce the structure and function of HMGB1 and its mechanism of action in SCI. Clarifying the functions of HMGB1 may provide insight into the links between SCI and various brain regions.