No abstract

Multiple sclerosis (MS) encompasses a chronic, irreversible, and predominantly immune-mediated disease of the central nervous system that leads to axonal degeneration, neuronal death, and several neurological symptoms. Although various immune therapies have reduced relapse rates and the severity of symptoms in relapsing-remitting MS, there is still no cure for this devastating disease. In this brief review, we discuss the role of mitochondria dysfunction in the progression of MS, focused on the possible role of Nrf2 signaling in orchestrating the impairment of critical cellular and molecular aspects such as reactive oxygen species (ROS) management, under neuroinflammation and neurodegeneration in MS. In this scenario, we propose a new potential downstream signaling of Nrf2 pathway, namely the opening of hemichannels and pannexons. These large-pore channels are known to modulate glial/neuronal function and ROS production as they are permeable to extracellular Ca2+ and release potentially harmful transmitters to the synaptic cleft. In this way, the Nrf2 dysfunction impairs not only the bioenergetics and metabolic properties of glial cells but also the proper antioxidant defense and energy supply that they provide to neurons.

No abstract

The present study evaluated the effect of magnesium sulfate (MgSO4) on forced swim-induced thermal hyperalgesia in male Sprague-Dawley rats. Two schemes of MgSO4 administration were used: a preemptive scheme (100 mg/kg i.p. before each forced swim) and a therapeutic scheme (a single dose of 100 mg/kg, 24 hours after the final forced swim); pharmacological controls received normal saline. Thermal nociception was determined using the hot plate test, and lumbar spinal levels of nitric oxide (NO) metabolites were measured. Thermal hyperalgesia was present in forced swim animals treated with saline before each forced swim, but absent in forced swim animals preemptively treated with MgSO4. We could not determine an anti-hyperalgesic effect of the therapeutic scheme since MgSO4 tended to produce analgesia when administered one hour before the hot plate test, probably due to an acute stress response caused by the injection. On the other hand, non-stressed animals preemptively treated with MgSO4 displayed significantly higher levels of NO metabolites than forced swim animals preemptively treated with MgSO4 or saline and non-stressed animals preemptively treated with saline. The results suggest that MgSO4 can prevent the development of persistent pain states, but is unable to revert already established ones, a potential feature in patients suffering from anxiety, depression and chronic stress exposure; likewise, they indicate that the effect of MgSO4 on nociception is independent of an induction of NO synthesis.