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Review

Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury

by
Femke Mussen
1,2,†,
Jana Van Broeckhoven
2,3,†,
Niels Hellings
2,3,
Melissa Schepers
1,2,4,* and
Tim Vanmierlo
1,2,4,*
1
Department of Neuroscience, Biomedical Research Institute BIOMED, Hasselt University, 3590 Diepenbeek, Belgium
2
University MS Center (UMSC) Hasselt-Pelt, Hasselt University, 3500 Hasselt, Belgium
3
Department of Immunology and Infection, Biomedical Research Institute BIOMED, Hasselt University, 3590 Diepenbeek, Belgium
4
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6229ER Maastricht, The Netherlands
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2023, 24(9), 8135; https://doi.org/10.3390/ijms24098135
Submission received: 14 April 2023 / Revised: 27 April 2023 / Accepted: 29 April 2023 / Published: 2 May 2023
(This article belongs to the Special Issue Role of Phosphodiesterase in Biology and Pathology 2.0)
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Abstract

Traumatic spinal cord injury (SCI) is characterized by severe neuroinflammation and hampered neuroregeneration, which often leads to permanent neurological deficits. Current therapies include decompression surgery, rehabilitation, and in some instances, the use of corticosteroids. However, the golden standard of corticosteroids still achieves minimal improvements in functional outcomes. Therefore, new strategies tackling the initial inflammatory reactions and stimulating endogenous repair in later stages are crucial to achieving functional repair in SCI patients. Cyclic adenosine monophosphate (cAMP) is an important second messenger in the central nervous system (CNS) that modulates these processes. A sustained drop in cAMP levels is observed during SCI, and elevating cAMP is associated with improved functional outcomes in experimental models. cAMP is regulated in a spatiotemporal manner by its hydrolyzing enzyme phosphodiesterase (PDE). Growing evidence suggests that inhibition of cAMP-specific PDEs (PDE4, PDE7, and PDE8) is an important strategy to orchestrate neuroinflammation and regeneration in the CNS. Therefore, this review focuses on the current evidence related to the immunomodulatory and neuroregenerative role of cAMP-specific PDE inhibition in the SCI pathophysiology.
Keywords: traumatic spinal cord injury; cAMP; phosphodiesterases; neuroinflammation; regeneration traumatic spinal cord injury; cAMP; phosphodiesterases; neuroinflammation; regeneration

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MDPI and ACS Style

Mussen, F.; Broeckhoven, J.V.; Hellings, N.; Schepers, M.; Vanmierlo, T. Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury. Int. J. Mol. Sci. 2023, 24, 8135. https://doi.org/10.3390/ijms24098135

AMA Style

Mussen F, Broeckhoven JV, Hellings N, Schepers M, Vanmierlo T. Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury. International Journal of Molecular Sciences. 2023; 24(9):8135. https://doi.org/10.3390/ijms24098135

Chicago/Turabian Style

Mussen, Femke, Jana Van Broeckhoven, Niels Hellings, Melissa Schepers, and Tim Vanmierlo. 2023. "Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury" International Journal of Molecular Sciences 24, no. 9: 8135. https://doi.org/10.3390/ijms24098135

APA Style

Mussen, F., Broeckhoven, J. V., Hellings, N., Schepers, M., & Vanmierlo, T. (2023). Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury. International Journal of Molecular Sciences, 24(9), 8135. https://doi.org/10.3390/ijms24098135

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