These results aid optimization of the time window for RIPostC use and offer novel insight into, and a better understanding of, the protective mechanism of autophagy in limb RIPostC.
White matter (WM) is an essential component of the human brain accounting for nearly 40% of total volume. 1 Functionally, WM plays an important role in neural signal transmission and communication within the brain. WM integrity is important in long-term recovery after stroke and small-vessel disease. 2,3 Unfortunately, WM injury is prevalent in nearly half of all cases of stroke and TBI. 4,5 Moreover, WM is extremely susceptible to ischemia as there is little collateral circulation and limited blood supply in this region. WM injury impairs Summary Introduction: The neuroprotective effects of hypothermia in acute ischemic stroke are well documented. However, the mechanisms involved in the effects remain to be clearly elucidated and the role of hypothermia on long-term white matter integrity after acute ischemic stroke has yet to be investigated.
Aims:To investigate the role of mild focal hypothermia on long-term white matter (WM) integrity after transient cerebral ischemia.Results: Mild focal hypothermia treatment immediately after ischemic stroke significantly promotes WM integrity 28 days after the occlusion of the middle cerebral artery (MCAO) in mice. Higher integrity of white matter, lower activation of total microglia, less infarct volume, and better neurobehavioral function were detected in hypothermia-treated mice compared to normothermia-treated mice. Furthermore, we found that hypothermia could decrease detrimental M1 phenotype microglia and promote healthy M2 phenotype microglia. In vitro, results also indicated that hypothermia promoted oligodendrocytes differentiation and maturation after oxygen glucose deprivation.Conclusion: Hypothermia promotes long-term WM integrity and inhibits neuroinflammation in a mouse model of ischemic brain injury.
K E Y W O R D Shypothermia, microglia, neuroprotection, stroke, white matter
Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.