Gastrodin alleviates NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in trigeminal ganglion.

BACKGROUND: Increasing evidence highlights the involvement of metabolic disorder and calcium influx mediated by transient receptor potential channels in migraine; however, the relationship between these factors in the pathophysiology of migraine remains unknown. Gastrodin is the major component of the traditional Chinese medicine Tianma, which is extensively used in migraine therapy. PURPOSE: Our work aimed to explore the analgesic action of gastrodin and its regulatory mechanisms from a metabolic perspective. METHODS/RESULTS: After being treated with gastrodin, the mice were given nitroglycerin (NTG) to induce migraine. Gastrodin treatment significantly raised the threshold of sensitivity in response to both mechanical and thermal stimulus evidenced by von Frey and hot plate tests, respectively, and decreased total contact numbers in orofacial operant behavioral assessment. We found that the expression of transient receptor potential melastatin 2 (TRPM2) channel was increased in the trigeminal ganglion (TG) of NTG-induced mice, resulting in a sustained Ca2+ influx to trigger migraine pain. The content of succinate, a metabolic biomarker, was elevated in blood samples of migraineurs, as well as in the serum and TG tissue from NTG-induced migraine mice. Calcium imaging assay indicated that succinate insult elevated TRPM2-mediated calcium flux signal in TG neurons. Mechanistically, accumulated succinate upregulated hypoxia inducible factor-1α (HIF-1α) expression and promoted its translocation into nucleus, where HIF-1α enhanced TRPM2 expression through transcriptional induction in TG neurons, evidenced by luciferase reporter measurement. Gastrodin treatment inhibited TRPM2 expression and TRPM2-dependent Ca2+ influx by attenuating succinate accumulation and downstream HIF-1α signaling, and thereby exhibited analgesic effect. CONCLUSION: This work revealed that succinate was a critical metabolic signaling molecule and the key mediator of migraine pain through triggering TRPM2-mediated calcium overload. Gastrodin alleviated NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in TG neurons. These findings uncovered the anti-migraine effect of gastrodin and its regulatory mechanisms from a metabolic perspective and provided a novel theoretical basis for the analgesic action of gastrodin.

Surgical anatomy of sigmoid sinus with evaluation of its venous dominance for advances in preoperative planning.

Microvascular decompression (MVD) is a widely adopted neurosurgery in treating cranial nerve diseases providing long-term pain relief. Improving surgical techniques has been a focus of recent studies. Venous structures such as the sigmoid sinus are essential to protect, and whose risk of destruction during surgery increases with size. The medical records of patients who went through MRI ahead of MVD surgery between Dec 2020 and Dec 2021 were reviewed. Section area of sigmoid sinus calculated from the MRI plane of auditory nerve showed a right dominance of the sinus. The improved method concerning the relationship between affected side and the dominant sigmoid sinus offered a better bone window and surgical field by planning the operation incision in advance. Intraoperative adjustment of the bone flap was avoided, and the risk of destructing the sigmoid sinus was reduced.

Microvascular decompression for young onset primary trigeminal neuralgia: a single-center experience.

This study aims to explore the causes of primary young onset trigeminal neuralgia (TN) and the clinical outcomes of these patients. From May 2015 to December 2020, 19 primary TN patients with onset age under 30 years underwent microvascular decompression (MVD) in Nanjing Drum Tower Hospital. In this study, the clinical characteristics, surgical outcomes, and postoperative complications of these patients were analyzed retrospectively. Of the 19 patients, 5 were males and 14 were females, and the pain was located on the right side in 10 cases (52.6%). Vascular compression was observed in 17 patients, including 14 cases of superior cerebellar artery (SCA) alone, 2 cases of superior petrosal vein (SPV) alone, and 1 case of SCA and SPV combined. Two patients had no neurovascular conflict, and nerve combing was performed. After surgery, 18 patients got immediate pain relief; 1 patient improved but still had occasional pain. With a mean follow-up of 42.7 ± 22.3 months, one patient was found to have a relapse 45 months after MVD. Surgical complications including mild facial numbness in two patients and hearing impairment in one patient. Neurovascular compression is the main cause of young onset primary TN, and the most commonly encountered vascular was SCA. MVD is a safe and effective treatment for these patients.

Analysis on the physiological changes of residents before and during the COVID-19 pandemic: A cross-sectional study.

People's lifestyles have changed dramatically during the coronavirus disease 2019 (COVID-19) pandemic, yet data on physical examinations in the Chinese population before and during the pandemic are rarely reported. The study was based on the data from the physical examination center of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. We collected the data of physical examinations information between January 2017 and March 2022. The data of participants before December 31, 2019 were classified as "before COVID-19 pandemic group," while data after December 31, 2019 were classified as "during COVID-19 pandemic group." We used t-test and χ2  test to compare the differences before and during COVID-19 pandemic. A total of 72 257 individuals participated in the physical examinations, and finally retained 65 629 individuals for analysis. During the COVID-19 pandemic, body mass index (BMI), high-density lipoprotein, total cholesterol levels, as well as pulmonary nodule and thyroid nodule proportion of participants were higher than those before the pandemic, and the levels of systolic blood pressure and diastolic blood pressure of participants were lower than those before the pandemic. Ongoing assessment and surveillance are necessary to assess whether lifestyle changes caused by the COVID-19 pandemic are likely to increase chronic disease risk in the future.

miR-212-5p Suppresses Glioma Development via Targeting SUMO2.

Recently, increasing studies have suggested that miRNAs play a significant role in the occurrence and development of glioma. More researches are needed to explore the role of miRNAs in glioma, which will help to find new therapeutic targets. miR-212-5p has been reported to be involved in the progression in many cancers. However, whether miR-212-5p has a regulative effect on glioma remains un clear. In this study, we aimed to explore the effect of miR-212-5p on glioma development and its mechanism. Here, we demonstrated that miR-212-5p was lowly expressed in glioma cell. miR-212-5p suppressed the glioma cell proliferation, inhibited the migratory and invasive capabilities and promoted apoptosis in glioma cells. Besides, miR-212-5p also inhibited tumor growth in vivo. We found small ubiquitin-like modifier 2 (SUMO2) was the target of miR-212-5p, and miR-212-5p suppressed SUMO2 expression to regulate the proliferation, migration, and apoptosis of glioma cells. These findings indicated that miR-212-5p may be a possible therapeutic target for the treatment for glioma.

MiR-455-5p Attenuates Cerebral Ischemic Reperfusion Injury by Targeting FLT3.

Cerebral ischemia-reperfusion (I/R) injury is a terrible disease which results in the dysfunction and structural damage of brain tissues. Growing evidence implies that miR-455-5p is implicated in the regulation of pathogenesis of several diseases. The aim of this study is to reveal the role of miR-455-5p in cerebral I/R injury and the regulatory mechanism. We established a vitro model by inducing SH-SY5Y and PC-12 cells with oxygen-glucose deprivation and reoxygenation. The experimental cerebral I/R rat model was established by middle cerebral artery occlusion operation. The findings indicated that miR-455-5p expression was downregulated in oxygen-glucose deprivation and reoxygenation induced cells and I/R rat model. In addition, miR-455-5p upregulation inhibited SH-SY5Y cell apoptosis and cerebral damage, whereas miR-455-5p silencing promoted SH-SY5Y cell apoptosis and cerebral damage. Mechanistically, luciferase reporter assay corroborated that miR-455-5p could bind with feline mcDonough sarcoma-like tyrosine kinase 3 (FLT3) mRNA. However, the role of FLT3 in cerebral I/R injury was rarely investigated. Real-time polymerase chain reaction revealed that FTL3 expression was negatively regulated by miR-455-5p. FTL3 upregulation reversed the inhibitory effects of miR-455-5p upregulation on PC-12 and SH-SY5Y cell apoptosis. Therefore, our study verified that miR-455-5p improved cerebral I/R injury by targeting FLT3, which suggests a potential new target for the prevention of cerebral I/R injury.

Therapeutic effect of intensive glycemic control therapy in patients with traumatic brain injury: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hyperglycemia is associated with dismal outcomes in patients with traumatic brain injury (TBI), which is frequently treated with insulin therapy. In this study, a systematic review and meta-analysis of the published randomized controlled trials (RCTs) was performed to assess the safety and efficacy of intensive glycemic control (IGC) versus conventional glycemic control (CGC) for patients following TBI. METHODS: Databases, including PubMed, Embase, and the Cochran database, were retrieved up to January 2018. The outcomes evaluated in this study included mortality, neurological outcome, infection rate, hypoglycemia episode, and length of stay (LOS) in intensive care unit (ICU). The enrolled trials were analyzed using the Review Manager 5.3 software. RESULTS: A total of 7 randomized controlled trials (RCTs) involving 1013 cases were enrolled in this study, and the results indicated no significant difference in 6-month mortality (risk ratio [RR], 0.92; 95% confidence interval [CI] 0.76-1.10; P = .34). Subsequently, IGC was associated with a better neurological outcome (RR, 1.22; 95% CI 1.05-1.43; P = .01), lower infection rate (RR, 0.65; 95% CI 0.51-0.82; P = .0003) and shorter LOS in ICU (mean difference [MD] = -1.37; 95%CI = -2.11, -0.63; P = .0003). In addition, IGC would also increase the risk of hypoglycemia episode (RR, 4.53; 95% CI 2.18-9.42; P < .001). CONCLUSIONS: IGC plays a protective role in improving neurological outcome, decreasing infection rate and reducing the LOS in ICU. However, IGC therapy can also remarkably increase the risk of hypoglycemia, but it will not affect the mortality in TBI patients.