C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Neural Regeneration Research, 2025 · DOI: https://doi.org/10.4103/NRR.NRR-D-24-00119 · Published: July 29, 2024

Simple Explanation

Spinal cord injury (SCI) leads to permanent damage and inflammation in the central nervous system due to its limited ability to repair itself. The CCL2/CCR2 pathway plays a significant role in the inflammatory response and recruitment of immune cells after SCI. Targeting this pathway could be a new way to treat SCI. CCL2/CCR2 axis generally elevates SCI severity by recruiting immune cells to the site of injury, stimulating inflammatory cells such as microglia and macrophages, which in turn trigger neuronal death and amplify the inflammatory response, exacerbating nerve damage. The expression level of CCL2 rises dramatically in the acute and subacute phases following SCI, revealing that CCL2/CCR2 could serve as a target for the prevention and treatment of SCI.

Study Duration

Not specified

Participants

Animal models

Evidence Level

Review

Key Findings

1
The CCL2/CCR2 axis recruits immune cells to the injury site, stimulating microglia and macrophages, which exacerbates the inflammatory response and nerve damage, worsening SCI.
2
CCL2, released by activated astrocytes after SCI, acts on microglia and neurons through small extracellular vesicles (sEVs) targeting the CCR2 receptor, leading to neuronal apoptosis and promoting microglial activation.
3
Targeting the CCL2/CCR2 axis via siRNA, CCR2 antagonists, or stem cell therapy can modulate the inflammatory response, glial scar formation, and neuronal death after SCI, offering potential therapeutic strategies.

Research Summary

This review examines the therapeutic strategies targeting the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis, along with the regenerative and repair mechanisms linking the axis to spinal cord injury. The CCL2/CCR2 axis modulates the PI3K/Akt, JNK, and the Bcl2/Bax/caspase-3 signaling pathways to affect apoptosis, which ultimately has consequences for SCI recovery. Stem cell treatment, which uses stem cells’ inherent capacity for regeneration. By secreting cytokines while regulating the cell state, mesenchymal stem cells reduce the creation of nerve scars, regulate inflammatory responses, and promote axon and vascular regeneration, therefore offering a new avenue for SCI therapy

Practical Implications

Targeted Therapies

Developing drugs or therapies that specifically target the CCL2/CCR2 axis could lead to new treatments for spinal cord injury.

Combination Therapies

Combining CCL2/CCR2-targeted therapies with other treatments, such as stem cell therapy or anti-inflammatory drugs, may provide a more effective approach to SCI treatment.

Personalized Medicine

Understanding the specific role of the CCL2/CCR2 axis in individual patients could allow for more personalized and effective treatment strategies.

Study Limitations

1
Lack of clinical studies focusing on the CCL2/CCR2 axis in spinal cord injury.
2
Challenges related to the promiscuity of the CCL2/CCR2 axis and selecting the best target (CCL2 or CCR2).
3
Uncertainty regarding how the CCL2/CCR2 axis influences spinal cord injury and the precise mechanisms involved in inflammatory responses and neuroprotection.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury