Protective role of ethyl pyruvate in spinal cord injury by inhibiting the high mobility group box-1/toll-like receptor4/nuclear factor-kappa B signaling pathway

Frontiers in Molecular Neuroscience, 2022 · DOI: 10.3389/fnmol.2022.1013033 · Published: September 16, 2022

Simple Explanation

Spinal cord injury (SCI) often leads to paralysis, and its recovery is hindered by chronic inflammation and axonal regeneration difficulties. Ethyl pyruvate (EP), a pyruvate derivative, possesses anti-inflammatory and neuroprotective properties that can potentially aid in SCI treatment. HMGB1, a nuclear protein mediator, triggers inflammation, activates astrocytes, and promotes glial scar formation. Ethyl pyruvate can inhibit HMGB1 protein, thus modulating the HMGB1/TLR4/NF-κB signaling pathway and reducing chronic inflammation after SCI. This paper explores how ethyl pyruvate potentially works to reduce chronic inflammation following SCI, suggesting that it could serve as a therapeutic agent for SCI.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level 5, Mini Review

Key Findings

1
Ethyl pyruvate (EP) inhibits the expression of various inflammatory mediators and eliminates the release of oxidative stress factors, thus exerting potent anti-inflammatory roles.
2
EP can significantly inhibit astrocytic proliferation and reduce the formation of glial scar, which is a major obstacle in SCI treatment.
3
Ethyl pyruvate (EP) treatment reduced the proliferation of over-activated astrocytes, prevented the neuroinflammation development, and promoted the axonal growth, along with the restoration of hind limb function in the SCI animal model.

Research Summary

Spinal cord injury (SCI) presents a significant medical challenge due to the chronic inflammation that impedes recovery and the formation of glial scars by astrocytes, which hinder axonal regeneration. Activated astrocytes contribute to these adverse effects by releasing cytokines and exacerbating glial scars. Extracellular HMGB1 stimulates astrocytes, triggers cell inflammation, and aggravates glial scars. The TLR4 receptor on astrocyte membranes binds to HMGB1, activating I-κB kinase, which stimulates NF-κB and initiates downstream inflammatory responses. Ethyl pyruvate (EP), a stable anti-inflammatory and neuroprotective agent, can effectively mitigate astrocyte proliferation and inflammatory responses by inhibiting the HMGB1/TLR4/NF-κB pathway, enhancing functional recovery in SCI patients. EP represents a promising treatment avenue for SCI.

Practical Implications

Therapeutic Potential for SCI

Ethyl pyruvate (EP) shows promise as a therapeutic agent for spinal cord injury (SCI) due to its anti-inflammatory and neuroprotective properties.

Targeting HMGB1 Pathway

The HMGB1/TLR4/NF-κB signaling pathway is a critical target for intervention in SCI, and EP's ability to inhibit this pathway suggests a potential mechanism for mitigating inflammation and promoting recovery.

Reducing Glial Scar Formation

EP's ability to inhibit astrocytic proliferation and reduce glial scar formation could improve axonal regeneration and functional outcomes in SCI patients.

Study Limitations

1
Further studies need to unravel other possible mechanisms mediated by EP
2
Elucidation of probable side eﬀects before being employed in the clinical setting
3
The speciﬁc interaction between HMGB1 and its receptors is unclear, and needs further studies.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury