Cerebral edema (CE) exerts an important effect on brain injury after traumatic brain injury (TBI). Upregulation of transient receptor potential melastatin 4 (TRPM4) in vascular endothelial cells (ECs) results in damage to capillaries and the blood-brain barrier (BBB), which is critical for the development of CE. Many studies have shown that 9-phenanthrol (9-PH) effectively inhibits TRPM4. The current study aimed to investigate the effect of 9-PH on reducing CE after TBI. In this experiment, we observed that 9-PH markedly reduced brain water content, BBB disruption, proliferation of microglia and astrocytes, neutrophil infiltration, neuronal apoptosis and neurobehavioral deficits. At the molecular level, 9-PH significantly inhibited the protein expression of TRPM4 and MMP-9, alleviated the expression of apoptosis-related molecules and inflammatory cytokines, such as Bax, TNF-α and IL-6, near injured tissue, and diminished serum SUR1 and TRPM4 levels. Mechanistically, treatment with 9-PH inhibited activation of the PI3K/AKT/NF-kB signaling pathway, which was reported to be involved in the expression of MMP-9. Taken together, the results of this study indicate that 9-PH effectively reduces CE and alleviates secondary brain injury partly through the following possible mechanisms: ①9-PH inhibits TRPM4-mediated Na + influx and reduces cytotoxic CE; ②9-PH hinders the expression and activity of MMP-9 by inhibiting the TRPM4 channel and decreases disruption of the BBB, thereby preventing vasogenic cerebral edema. ③9-PH reduces further inflammatory and apoptotic damage to tissues.
Objective This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder.Methods Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration.Results The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week.Conclusion PMTS is safe and effective in improving insomnia disorders.
Background Sulfonylurea receptor-1(Sur1) and transient receptor potential melastatin 4(Trpm4) are implicated in acute brain injury. We determine whether serum Sur1 and Trpm4 concentrations are associated with spontaneous intracerebral hemorrhage(ICH) related perihematomal edema(PHE) and clinical outcome after ICH. Methods Serum Sur1 and Trpm4 concentrations were measured in 51 healthy controls and 51 patients with ICH. modified Rankin Scale (mRS) score and non-contrast computed tomography (NCCT) were recorded to assess perihematomal edema (PHE) severity. Modified Rankin Scale(mRS) score of 4–6 at 3 months after ICH was defined as an unfavorable outcome. Results Serum Sur1 and Trpm4 concentrations were substantially higher in patients with ICH than in controls. Peak PHE volume was positively correlated with baseline Sur1(r = 0.302, p = 0.031) and more significant related to peak Sur1(0.346, 0.013). Under receiver operating characteristic curve, peak Sur1 levels remained as an independent predictor of poor outcome (OR1.574, 95% CI, 1.144 to 2.165). Conclusions Elevated serum Sur1 levels are related to PHE severity and are independently associated with poor prognosis after ICH, indicating that serum Sur1 may have the potential to be a prognostic biomarker of ICH.
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