<p>Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments</p>

Abstract

Background: The myelin sheath can be damaged by genetic and/or environmental factors, leading to demyelinating diseases, for which effective treatments are lacking. Recently, cyclooxygenase-2 (COX-2) overexpression was detected in demyelinating lesions both in patients and animal models, opening an avenue for promoting endogenous remyelination. The aim of this study was to investigate the therapeutic effect of celecoxib, a selective COX-2 inhibitor, against demyelination in a zebrafish model. Methods: The biotoxicity of celecoxib was evaluated on zebrafish embryos. Metronidazole was used to deplete the oligodendrocytes in Tg (mbp:nfsB-egfp) transgenic fish. Celecoxib was then administered both in larvae and adults. The regeneration of the myelin sheath and the underlying mechanisms were explored by immunohistochemistry, flow cytometry, Western blot analysis, quantitative real-time polymerase chain reaction, and behavioral test. Results: Celecoxib had low in vivo toxicity. A stable and practical demyelination model was established by metronidazole induction. Following celecoxib treatment, the number of oligodendrocytes was increased significantly and the concentric structure of the myelin sheath reappeared. The locomotor ability was notably improved and was close to its physiological levels. The expression of arg1, mrc1, il-10, and il-4 was upregulated, while that of il-1β, il-12, tnf-α, il-6, caspase-3 and caspase-7 was downregulated. Conclusion: Inhibition of COX-2 contributed to the transformation of microglia/macrophages from the M1 to the M2 phenotype, improved the inflammatory microenvironment, and suppressed caspase-dependent apoptosis, thus exerting a therapeutic effect against demyelination.

Perioperative Suppression of Schwann Cell Dedifferentiation Reduces the Risk of Adenomyosis Resulting from Endometrial–Myometrial Interface Disruption in Mice

“…Estrogen, coupled with PGE 2 , could also induce hyperperistalsis in the EMI, which could further exacerbate injury to the SCs as well as compromise the barrier function of EMI, making it more receptive to invading cells. Additionally, COX-2, in itself, also plays an important role in SCs demyelination [ 72 ].…”

Role of diffusion kurtosis imaging for detecting brain microstructural changes in complete remission childhood survivors undergoing chemotherapy for acute lymphoblastic leukemia

“…Consequently, if demyelination can be detected quickly, it will help prevent axonal damage when remyelination is promoted. There is increasing evidence that in ammation is necessary for myelin repair; recent studies have found that celecoxib has antidemyelinating effects and promotes myelin regeneration by improving the immune and in ammatory microenvironment [24].…”

DHA and EPA Alleviate Epileptic Depression in PTZ-Treated Young Mice Model by Inhibiting Neuroinflammation through Regulating Microglial M2 Polarization and Improving Mitochondrial Metabolism

“…M1 polarization is characterized by the secretion of proinflammatory cytokines and an increased expression of iNOS. The M1 microglial phenotype has been suggested as a cause or consequence of epilepsy [10,13,14] and is conducive to the onset of depression [8]. Polarization of microglia into the M2 phenotype, characterized by a higher expression of arginase-1 (Arg1), facilitates the release of various anti-inflammatory factors to enhance neuronal protection [15].…”