Melatonin ameliorates spinal cord injury by suppressing the activation of inflammasomes in rats

Abstract

Background The activation of inflammasomes plays an important role in the pathogenesis of spinal cord injury (SCI). In addition, the administration of melatonin (MT) has been shown to suppress the activation of inflammasomes. In this study, we aimed to investigate the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI. Methods Basso‐Beattie‐Bresnahan (BBB) locomotion scaling was conducted to evaluate the therapeutic effect of MT on post‐SCI locomotion recovery. In addition, the measurement of spinal cord water content was performed together with Nissl staining to evaluate the protective effect of MT against SCI. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry (IHC) assay, Western blot analysis, and real‐time polymerase chain reaction (PCR) were also conducted to clarify the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI. Results BBB scores of SCI + MT rats were increased compared with the BBB scores of SCI rats, thus confirming the beneficial role of MT treatment in post‐SCI functional recovery. Meanwhile, the administration of MT could alleviate SCI by reducing spinal cord water content and by exerting a neuroprotective effect on motor neurons. Furthermore, in the treatment of SCI, MT also attenuated cell apoptosis. Moreover, the relative expression of NLRP3, interleukin‐1β (IL‐1β), and caspase‐1 were markedly elevated in the SCI group compared with that in the sham group, while the administration of MT reduced the expression of NLRP3 in SCI rats. Conclusions MT treatment accelerated the recovery of SCI by suppressing the activation of inflammasomes.

Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson’s Disease

“…Recent studies on mouse brain injury and major depressive disorder models showed that the anti-inflammatory effect of melatonin was partially attributed to the suppression of NLRP3 inflammasome activity, where melatonin reduced the expression of NLRP3 inflammasome components and the protein levels of IL-1β. [16][17][18] However, the inhibitory effect of melatonin on NLRP3 inflammasome activation in PD per se has not been studied.…”

Retracted Article: Melatonin protects spinal cord injury by up-regulating IGFBP3 through the improvement of microcirculation in a rat model

“…[16][17][18][19] It is also considered that melatonin can provide protection against SCI by decreasing SCI-induced oxidative injury in rat kidney, 20 attenuating calpain upregulation, axonal damage and neuronal death, 21 as well as reducing SCI-induced functional and biochemical changes in rat urinary bladder. 22 Melatonin can inuence several molecular signaling pathways, such as PI3K/AKT/mTOR signaling, 23 Wint/b-catenin signaling 24 and the activation of inammasome, 25 during this process. However, the relationship between melatonin and IGFBP3 in the SCI development is still unknown.…”

Neuroprotective role of icariin in experimental spinal cord injury via its antioxidant, anti‑neuroinflammatory and anti‑apoptotic properties

“…inflammation is a crucial factor in secondary damage following Sci, and anti-inflammatory therapy contributes to recovery from Sci (34,35). nrf2 is a factor that regulates the transcription of cytoprotective genes, including Ho-1 and NQO1, thereby playing a pivotal role in anti-inflammatory response (36).…”