Review: The role of HMGB1 in spinal cord injury

Frontiers in Immunology, 2023 · DOI: 10.3389/fimmu.2022.1094925 · Published: January 12, 2023

Simple Explanation

High mobility group box 1 (HMGB1) protein acts both inside the cell nucleus and outside as an inflammatory signal. After spinal cord injury (SCI), HMGB1 is released and participates in the injury's processes. HMGB1 can worsen inflammation by activating certain immune cells (M1 microglia) and controlling inflammatory factor production, leading to nerve cell death. However, some studies indicate HMGB1 aids in neuron survival, regeneration, and motor function recovery. This article reviews how HMGB1 is released, when it moves within cells, and its role in spinal cord injury. It also identifies challenges and provides a foundation for future research.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
HMGB1 expression increases rapidly after SCI and lasts for an extended period, potentially influencing the severity and recovery process. It remains elevated even in chronic stages, warranting further investigation into its mechanisms and effects.
2
HMGB1 translocates from the nucleus to the cytoplasm and extracellular matrix after SCI. The specific timing and mechanisms of this translocation remain unclear.
3
HMGB1 can promote the growth of neuronal axons and induce the differentiation of neural stem cells after SCI.

Research Summary

HMGB1, a nuclear protein, is structurally divided into A-box, B-box, and acidic C-terminus. In a resting state, it regulates key nuclear activities. However, there are no related studies on the structural and functional changes in HMGB1 after SCI. After SCI, HMGB1 expression increases in neurons, microglia/macrophages, and ependymal cells and remains elevated throughout acute, subacute, and chronic stages, affecting the severity and recovery process. HMGB1 increases in the nucleus and is then released from the nucleus to the cytoplasm and extracellular matrix. HMGB1 that is secreted and released into the extracellular space can induce the migration of inﬂammatory cells, aggravate the inﬂammatory response by regulating the activation of microglia to the M1 phenotype, and regulate the expression of inﬂammatory factors through RAGE and TLR2/4.

Practical Implications

Therapeutic Target

HMGB1 represents a potential therapeutic target for SCI. Inhibiting HMGB1 can reduce nerve inflammation and protect the spinal cord. Promoting HMGB1 can be used to protect neurons, promote neuronal regeneration, and induce neuronal differentiation to promote the recovery of SCI.

Treatment Strategies

Treatment with hyperbaric oxygen, shikorin, glycyrrhizin, Higenamine, ethyl pyruvate, Catalpol, Dihydrotanshinone I, mir-34a, anti-HMGB1 mAb, etc., can reduce inflammation and reduce spinal cord oedema, protect spinal cord neurons and promote functional recovery after SCI by downregulating the expression of HMGB1 and NF-kB

Future Research Directions

Future research should focus on the different roles of HMGB1 in the nucleus and extracellular space after SCI, clarifying the specific secretion and release mechanism, and determining the spatiotemporal relationship of HMGB1 expression, the protective effect on neurons, and the mechanism of promoting differentiation.

Study Limitations

1
The specific mechanisms by which HMGB1 protects injured neurons and promotes injury recovery are not clear.
2
Research on treating SCI by targeting HMGB1 is not sufficient, and its specific application scheme still needs to be further explored.
3
The specific time and node of translocation of HMGB1 from the nucleus to the cytoplasm and extracellular matrix have not been clarified.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury