Multifaceted Roles of cAMP Signaling in the Repair Process of Spinal Cord Injury and Related Combination Treatments

Frontiers in Molecular Neuroscience, 2022 · DOI: 10.3389/fnmol.2022.808510 · Published: February 23, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) leads to several issues like blood barrier damage, bleeding, oxidative stress, inflammation, scar formation and demyelination. These issues damage tissue and prevent nerve regeneration. cAMP signaling helps nerves grow and find their way. Increasing cAMP can improve nerve survival and regrowth after SCI. Treatments that target cAMP signaling have become more common. Combining cAMP treatments with other methods has shown better results for SCI recovery. Nanoparticles can carry agents to improve water solubility and cross the blood-spinal cord barrier. Bioscaffolds and hydrogels can release agents locally.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Stimulating intracellular cAMP activity significantly promotes neuronal survival and axonal regrowth after SCI.
2
cAMP signaling is involved in the regulation of glial cell function in the microenvironment of SCI, including macrophages/microglia, reactive astrocytes, and oligodendrocytes.
3
Combination treatments associated with cAMP signaling have been shown to exert synergistic effects on the recovery of SCI.

Research Summary

Spinal cord injury (SCI) results in multiple pathophysiological processes, including blood–spinal cord barrier disruption, hemorrhage/ischemia, oxidative stress, neuroinﬂammation, scar formation, and demyelination. cAMP signaling is vital for neurite outgrowth and axonal guidance. Stimulating intracellular cAMP activity signiﬁcantly promotes neuronal survival and axonal regrowth after SCI. Emerging progress focused on cAMP compartmentation provides researchers with new perspectives to understand the complexity of downstream signaling, which may facilitate the clinical translation of strategies targeting cAMP signaling for SCI repair.

Practical Implications

Combination Therapies

Combining cAMP-elevating agents with other treatments like immunomodulatory drugs, bioscaffolds, or cell transplantation can enhance recovery outcomes.

Targeted Drug Delivery

Using nanoparticles and bioscaffolds to deliver cAMP-elevating agents locally can improve their bioavailability and specificity while reducing systemic side effects.

cAMP Compartmentalization

Understanding the complexity of cAMP compartmentation can lead to the development of more precise molecules that target specific cAMP domains for SCI repair.

Study Limitations

1
Systemic elevation of cAMP may cause dysfunction of other cells and additional deleterious effects.
2
The intracellular mechanism of how cAMP promotes the polarization of macrophages/microglia remains unclear.
3
Research on whether cAMP signaling is related to growth supporting effects of astrocytic scars is still lacking.

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