The goal of this study was to evaluate the potential involvement of
melatonin in the activation of the nuclear factor erythroid 2-related factor 2 and
antioxidant-responsive
element (Nrf2-ARE) signaling pathway and the modulation of
antioxidant enzyme activity in an experimental model of
traumatic brain injury (TBI). In experiment 1, ICR mice were divided into four groups:
sham group, TBI group, TBI + vehicle group, and TBI +
melatonin group (n = 38 per group).
Melatonin (10mg/kg) was administered via an intraperitoneal (ip) injection at 0, 1, 2, 3, and 4h post-TBI. In experiment 2, Nrf2 wild-type (Nrf2(+/+) group) and Nrf2-knockout (Nrf2(-/-) group) mice received a TBI insult followed by
melatonin administration (10mg/kg, ip) at the corresponding time points (n = 35 per group). The administration of
melatonin after TBI significantly ameliorated the effects of the
brain injury, such as oxidative stress,
brain edema, and cortical neuronal degeneration.
Melatonin markedly promoted the translocation of Nrf2
protein from the cytoplasm to the nucleus; increased the expression of Nrf2-ARE pathway-related downstream factors, including
heme oxygenase-1 and
NAD(P)H: