Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Purpose: Intensive care unit-acquired weakness (ICUAW) is a severe neuromuscular complication that frequently occurs in patients with sepsis. The precise molecular pathophysiology of mitochondrial calcium uptake 1 (MICU1) and mitochondrial calcium uniporter (MCU) in ICUAW has not been fully elucidated. Here, we speculate that ICUAW is associated with MICU1:MCU protein ratio-mediated mitochondrial calcium ([Ca 2+ ] m ) uptake dysfunction. ⋯ However, MICU1 prophylactic overexpression reversed these effects by increasing the MICU1:MCU protein ratio. Conclusions: ICUAW is associated with impaired [Ca 2+ ] m uptake caused by a decreased MICU1:MCU protein ratio. MICU1 overexpression improves sepsis-induced skeletal muscle weakness and atrophy by ameliorating the [Ca 2+ ] m uptake disorder.
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Objective: Neurological complications after myocardial ischemia/reperfusion (IR) injury remain high and seriously burden patients and their families. Dexmedetomidine (Dex), an α 2 agonist, is endowed with analgesic-sedative and anti-inflammatory effects. Therefore, our study aims to explore the mechanism and effect of Dex on brain damage after myocardial IR injury. ⋯ Results: Dex was capable of reducing myocardial IR-induced brain damage including inflammatory factor secretion, blood-brain barrier disruption, neuronal edema, microglial activation, and acute cognitive dysfunction. However, the protective role of Dex was attenuated in HIF-1α knockout mice. Conclusion: Dex protects against myocardial IR-induced brain injury, and the neuroprotection of Dex is at least partially dependent on the activation of the HIF-1 pathway.