Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats

Ming Che Tsai, Wei Ju Chen, Ming Shi Tsai, Cheng Hsin Ching, Jih-Ing Chuang

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

The induction of oxidative stress and inflammation has been closely linked in traumatic brain injury (TBI). Transcriptional factors of signal transducers and activators of transcription (STAT) proteins are redox sensitive and participate in the regulation of cytokine signaling. Previous studies demonstrated that melatonin protects neurons through its antioxidative and anti-inflammatory effects in various neuropathological conditions. However, the effect of melatonin on STAT activity after TBI has not yet been explored. In this study, we used a controlled weight-drop TBI model and found that brain contusion induced oxidative stress (a decreased level of total glutathione and an increased ratio of oxidized glutathione to total glutathione), a reduction in STAT1 DNA-binding activity, and consequently neuronal loss in a contusion depth-dependent manner. A significant increased mRNA expression of suppressor of cytokine signaling (SOCS3), inducible nitric oxide synthetase (iNOS), and interleukine-6 (IL-6), but a decreased protein expression of protein inhibitor of activated STAT (PIAS1), was found 24 hr after brain contusion. SOCS3 and PIAS1 are endogenous negative regulators of STAT1. Moreover, the combination of intraperitoneal and local (presoaked in gelfoam and placed on the traumatic cortex) administration of melatonin had the most pronounced influence in inhibiting all effects except the PIAS1 downregulation induced by brain contusion. The results suggest that SOCS-3 upregulation and oxidative stress may contribute to the STAT1 inactivation after TBI. Melatonin protects neurons from TBI by reducing oxidative stress, STAT1 inactivation, and upregulation of SOCS-3 and pro-inflammatory cytokines.

Original languageEnglish
Pages (from-to)233-245
Number of pages13
JournalJournal of Pineal Research
Volume51
Issue number2
DOIs
Publication statusPublished - 2011 Sep 1

All Science Journal Classification (ASJC) codes

  • Endocrinology

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