Permanent functional deficits following
spinal cord injury (SCI) arise from both mechanical injury and from secondary tissue reactions involving
inflammation. The
mitogen-activated protein kinases (MAPKs) play a critical role in cell signaling and gene expression. MAPK family includes three major members:
extracellular signal regulated kinase (ERK), p38, and
c-Jun N-terminal kinase (JNK), representing three different signaling cascades. Moreover, various studies have clearly shown that high-mobility group box 1 (
HMGB1) protein is implicated as a putative danger signal involved in the pathogenesis of a variety of inflammatory conditions including autoimmunity,
cancer,
trauma and
hemorrhagic shock, and
ischemia-reperfusion injury. Recently, we have reported that the pineal secretory product
melatonin exerts important anti-inflammatory effects in an experimental model of SCI induced by the application of vascular clips (force of 24 g) to the dura after a four-level T5-T8
laminectomy. However, no reports are available on the effect of
melatonin on MAPK signaling pathways and
HMGB1 expression in SCI. The aim of the present study was to evaluate whether the
melatonin protective effect observed in SCI is related to the regulation of MAPK signaling pathways and
HMGB1 in mice. In this study we demonstrate the efficacy of treatment with the
melatonin in SCI in mice in reducing (a) motor recovery, (b) activation of MAPKs p38, JNK and ERK1/2, (c)
tumor necrosis factor-alpha expression, and (d) expression of
HMGB1. We propose that
melatonin's ability to reduce SCI in mice is also related to a reduction in MAPK signaling pathways and
HMGB1 expression.