Turkish Journal of Medical Sciences
Abstract
Background/aim: Every year, hundreds of thousands of people worldwide suffer from traumatic spinal cord injury (tSCI), which causes irreversible damage, edema, and inflammation. Despite its devastating impact, no safe and effective medication is available. Edema formation is one of the earliest pathological events in tSCI, beginning within minutes after injury. Cytotoxic edema progresses to vasogenic edema, exacerbating irreversible damage. Our study aimed to investigate a therapeutic approach targeting cytotoxic edema in the acute phase of tSCI to improve treatment outcomes. Aquaporins (AQPs) are crucial in edema formation and tSCI pathogenesis. Vasopressin, also known as the antidiuretic hormone, modulates Aqp expression and translocation by initiating cell signaling via vasopressin 1a receptor (V1aR) and vasopressin 2 receptor (V2R). We investigated the effects of two V1aR and V2R antagonists (relcovaptan and tolvaptan, respectively) on edema formation and Aqp expression in tSCI.
Materials and methods: Transcriptome analysis was performed on male Sprague Dawley rats that were traumatized to determine the effect of relcovaptan and tolvaptan after tSCI. Gene set enrichment analysis and bioinformatics approaches identified critical genes and signaling pathways associated with the drug treatment.
Results: According to our results, tolvaptan was not suitable for the treatment of tSCI. On the other hand, relcovaptan had multiple positive effects. These include not only the positive effect on edema, which is achieved by suppression of Aqp1, Aqp4, and Aqp11 expression, but also immunoregulation, neuroprotection, neuroregeneration, and osmoregulation via activator protein-1 and galanin.
Conclusion: Our study suggests that clinical application of relcovaptan may be a promising treatment option for improving tSCI.
Author ORCID Identifier
ŞEYMA İŞ: 0000-0002-5151-6758
DUYGU CEMAN: 0000-0003-0215-4233
MERİH İŞ: 0000-0002-5035-2229
NEŞE KESER: 0000-0002-6024-8855
ŞABAN TEKİN: 0000-0003-2641-6293
DOI
10.55730/1300-0144.6097
Keywords
Aquaporins, edema, relcovaptan, RNA sequencing, tolvaptan, traumatic spinal cord injury
First Page
1394
Last Page
1407
Publisher
The Scientific and Technological Research Council of Türkiye (TÜBİTAK)
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
İŞ, Ş, CEMAN, D, İŞ, M, KESER, N, & TEKİN, Ş (2025). Relcovaptan: a promising therapeutic agent in traumatic spinal cord injury that acts by modulating newly identified transcriptional regulators of aquaporins compared to tolvaptan. Turkish Journal of Medical Sciences 55 (6): 1394-1407. https://doi.org/10.55730/1300-0144.6097
