Mild hypothermia (MH) and edaravone (EDA) exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. However, whether MH and EDA exert synergistic effects against cerebral I/R injury remains unknown. The aim of the present study was to investigate the effects and mechanism of action of MH in combination with EDA in cerebral I/R injury. A rat cerebral I/R injury model was constructed by middle cerebral artery occlusion (MCAO) followed by reperfusion, and the mice were treated by MH, EDA or the inhibitor of the Nrf2 signaling pathway brusatol (Bru). It was observed that mice treated by MCAO had higher neurological deficit scores and oxidative stress levels, and low spatial learning and memory capacity; moreover, the CA1 region of the hippocampi of the mice exhibited reduced neuronal density and viability, and reduced mitochondrial dysfunction. However, MH in combination with EDA reversed the effects of MCAO, which were blocked by Bru injection. The levels of glutathione (GSH), GSH peroxidase, catalase and superoxide dismutase in rat ischemic hemisphere tissues were reduced by Bru. Western blotting demonstrated that the combined treatment with MH and EDA promoted the nuclear localization of Nrf2, and increased the levels of NAD(P)H quinone oxidoreductase and heme oxygenase (HO)-1. In conclusion, MH combined with EDA exerted synergistic neuroprotective effects against cerebral I/R injury involving changes in the Nrf2/HO-1 pathway.

The overall incidence rate of stroke is increasing worldwide. Inflammatory damage following a stroke is a leading cause for the poor prognosis and high disability rate observed in stroke patients. Microglia are considered to be the main causative agents of inflammatory injury following cerebral infarction, as they secrete various inflammatory cytokines and cytotoxic factors. The aim of the present study was to identify novel methods for attenuating inflammatory injury and improving the prognosis of stroke patients. Lipopolysaccharide-stimulated microglia were treated using propofol in vitro and a transient middle cerebral artery occlusion/reperfusion model was constructed in rats. Expression of cytotoxic factors, microglia proliferation and the neuroprotective effects of propofol were measured in vitro and in vivo. The in vitro studies demonstrated that propofol inhibits the expression of multiple cytotoxic factors, prevents structural changes to cytoskeletal proteins, and suppresses microglial migration via the adenosineA2b receptors. The results of the in vivo experiments revealed that propofol inhibits the abnormal proliferation of microglia, as well as reduces the expression levels of interleukin (IL)-6, IL-1β, tumor necrosis factor α, and the cytotoxic factor nitric oxide through the A2b receptor. In conclusion, propofol inhibited the excessive activation of microglia through the A2b receptor and attenuated the inflammatory injury following cerebral infarction. The current study may provide a reliable basis for further clinical studies on propofol and its putative role in improving the prognosis of patients with cerebral infarction.

Stroke is a cerebrovascular circulatory disorder and its high mortality rate represents a prominent threat to human health. Subsequent apoptosis and cytotoxicity are the main causes underlying the poor prognosis. Midazolam (MdZ) is a benzodiazepine drug that is clinically used during surgical procedures and for the treatment of insomnia, with a potential ability to treat stroke. The protective effect of MdZ was investigated on glutamate-induced cortical neuronal injuries in vitro and transient middle cerebral artery occlusion (tMcAO) rat models in vivo. Western blot analysis and semi quantitative RT-PcR were used to evaluate the potential underlying mechanisms. In vitro studies revealed that MdZ regulated apoptosis-associated gene expression and inhibited lactate dehydrogenase (LdH) release, protecting against neuronal damage. In vivo studies revealed that MdZ reduced LdH-induced neuronal damage by reducing LdH release from the peripheral blood, and brain tissue staining revealed that MdZ protected neurons during tMcAO. MdZ protected neurons under an ischemic environment by inhibiting LdH release and regulating apoptosis-associated gene expression to reduce cytotoxicity and apoptosis. These results provide a reliable basis for further studies on the effect of MdZ, to improve the prognosis of cerebral infarction.

Critical illness refers to the clinical signs of severe, variable and life-threatening critical conditions, often accompanied by insufficiency or failure of one or more organs. Bone health of critically ill patients is severely affected during and after ICU admission. Therefore, clinical work should focus on ICU-related bone loss, and early development and implementation of related prevention and treatment strategies: optimized and personalized nutritional support (high-quality protein, trace elements and intestinal prebiotics) and appropriate physiotherapy and muscle training should be implemented as early as possible after ICU admission and discharge. At the same time, the drug regulates excessive metabolism and resists osteoporosis.