Tat-NR2B9c attenuates oxidative stress via inhibition of PSD95-NR2B-nNOS complex after subarachnoid hemorrhage in rats.

Oxidative stress plays important roles in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Tat-NR2B9c has shown efficacy as a neuroprotective agent in several studies. Here, we identified the neuroprotective role of Tat-NR2B9c after SAH and its related mechanisms. The results showed that Tat-NR2B9c treatment attenuated oxidative stress, therefore alleviated neuronal apoptosis and neurological deficits after SAH. Tat-NR2B9c treatment could alleviate mitochondrial vacuolization induced by SAH. Compared to SAH + vehicle group, Tat-NR2B9c resulted in the decrease of Acetylated superoxide dismutase2 (Ac-SOD2), Bcl-2-associated X protein (Bax) and cleaved-caspase3 (CC3) protein expression, and the up-regulation of Sirtunin 3 (Sirt3) and Bcl-2 protein level. Moreover, Tat-NR2B9c attenuated excitotoxicity by inhibiting the interaction of PSD95-NR2B-nNOS. Our results demonstrated that Tat-NR2B9c inhibited oxidative stress via inhibition of PSD95-NR2B-nNOS complex formation after SAH. Tat-NR2B9c may serve as a potential treatment for SAH induced brain injury.

Efficacy and safety of acupuncture in the treatment of post-traumatic headache secondary to mild traumatic brain injury: A systematic evaluation and meta-analysis protocol of randomized controlled trials.

INTRODUCTION: Post-traumatic headache secondary to mild traumatic brain injury in patients has become an important factor in their prognosis. Due to the lack of effective pharmacological treatments, non-pharmacological interventions such as acupuncture are considered to have greater potential. However, the efficacy and safety of acupuncture treatment have not been clearly demonstrated. The purpose of this meta-analysis protocol is to investigate the effectiveness and safety of acupuncture in the treatment of headache secondary to mild traumatic brain injury. METHODS AND ANALYSIS: Seven English and Chinese databases will be selected and searched according to their respective search methods, spanning the period from database creation to April 2022, and the languages will be limited to English and Chinese. Only randomized controlled trials will be included. Study selection, data collection, and risk of bias control will be performed by two independent investigators. Any disagreements will be referred to a third independent investigator for decision and documentation. Revman software will be used to complete our meta-analysis, and risk of bias assessment, subgroup analysis, and sensitivity analysis will be performed to correct the results. Finally we will assess the reliability of our final results using the Recommended Guidelines Development Tool for Assessment. ETHICS AND DISSEMINATION: All data for this study will be obtained from published journals, so no ethical review will be required. The completed review will be published in a peer-reviewed journal and the findings will be further disseminated through presentation at an appropriate forum or conference.

Innovative emergency strategies for patients with severe traumatic brain injury: An IoT-based resource integration.

Severe traumatic brain injury patients are in critical condition, and rapid rescue is very important for prognosis. Currently, the resuscitation process is complex and it is difficult to get to the operating room quickly to target treatment. We present a new strategy based on the Internet of Things system to integrate complex first aid procedures for efficient and comprehensive rescuing of patients with severe traumatic brain injury. This system includes three modules: human sign monitoring equipment, emergency transport equipment, and a network diagnosis and treatment progress control center. The system not only supports the streamlining of rescue procedures but also transmits the patient's status and optimal treatment strategies in real-time by using an advanced Internet of Things system. After deploying the system in a hospital, we conducted a validation study to evaluate its feasibility and superiority in clinical use. The preliminary results of the study show that this system can significantly shorten the treatment time, which may help the prognosis of severe traumatic brain injury patients.

Intranasal Insulin Treatment Attenuates Metabolic Distress and Early Brain Injury After Subarachnoid Hemorrhage in Mice.

BACKGROUND: Intranasal administration of insulin to the brain bypasses the blood brain barrier (BBB) and can increase cerebral glucose uptake and prevent energy failure. Intranasal insulin treatment has shown neuroprotective effects in multiple central nervous system (CNS) lesions, but the effects of intranasal insulin on the metabolic and pathological process of subarachnoid hemorrhage (SAH) are not clear. This study is designed to explore the effects of intranasal insulin treatment on metabolic distress and early brain injury (EBI) after experimental SAH. METHODS: SAH model was built by endovascular filament perforation method in adult male C57BL/6J mice, and then, insulin was administrated via intranasal route at 0, 24, and 48 h post-SAH. EBI was assessed according to the neurological performance, BBB damage, brain edema, neuroinflammatory reaction, and neuronal apoptosis at each time point. To evaluate metabolic conditions, microdialysis was used to continuously monitor the real-time levels of glucose, pyruvate, and lactate in interstitial fluid (ISF) in living animals. The mRNA and protein expression of glucose transporter-1 and 3 (GLUT-1 and -3) were also tested by RT-PCR and Western blot in brain after SAH. RESULTS: Compared to vehicle, intranasal insulin treatment promoted the relative mRNA and protein levels of GLUT-1 in SAH brain (0.98 ± 0.020 vs 0.33 ± 0.016 at 24 h, 0.91 ± 0.25 vs 0.21 ± 0.013 at 48 h and 0.94 ± 0.025 vs 0.28 ± 0.015 at 72 h in mRNA/0.96 ± 0.023 vs 0.36 ± 0.015 at 24 h, 0.91 ± 0.022 vs 0.22 ± 0.011 at 48 h and 0.95 ± 0.024 vs 0.27 ± 0.014 at 72 h in protein, n = 8/Group, p < 0.001). Similar results were also observed in GLUT-3. Intranasal insulin reduced the lactate/pyruvate ratio (LPR) and increased ISF glucose level. It also improved neurological dysfunction, BBB damage, and brain edema and attenuated the levels of pro-inflammatory cytokines as well as neuronal apoptosis after SAH. CONCLUSIONS: The intranasal insulin treatment protects brain from EBI possibly via improving metabolic distress after SAH.

Bioinformatics analysis of microRNA profiles and identification of microRNA-mRNA network and biological markers in intracranial aneurysm.

Intracranial aneurysm (IA) is a kind of cerebrovascular disorder, which may result in the subarachnoid hemorrhage with high lethality and disability. The purpose of this study was to reveal the pathogenesis and identify novel biomarkers in IA.We processed the raw microRNA (miRNA) expression profile data of IA obtained from Gene Expression Omnibus. Then weighted correlation network analysis was performed to identify the hub miRNAs in IA. Target genes of hub miRNAs were predicted using multiR package. In addition, a protein-protein network as well as miRNA-mRNA network was constructed and functional and pathway enrichment analyses were done. Finally, the prediction value of hub miRNAs in IA was tested in validation set.Two modules that had relation with IA were identified and 10 hub miRNAs in each module with higher gene-module association were selected. The protein-protein network and miRNA-mRNA network contained 243 nodes and 1496 edges. Functional and pathway enrichment analyses showed that they were mainly enriched in cell cycle, cell proliferation, and PI3K/Akt signaling pathways. Besides, hsa-miR-191-3p, hsa-miR-423-5p, hsa-miR-424-5p, hsa-miR-425-3p were proven to be valuable in prediction IA occurrence.In a word, this study reveals hub miRNAs, target genes and pathways potentially participating in formation and development of IA and screens out some candidate biomarkers. Our findings provide some new perspectives for research and treatment of IA.

LncRNA RGMB-AS1 Promotes Glioma Growth and Invasion Through miR-1200/HOXB2 Axis.

BACKGROUND: Dysfunction of long noncoding RNA (lncRNA) is associated with tumorigenesis of various malignancies, including glioma. LncRNA RGMB-AS1 (RGMB antisense RNA 1) has been reported to participate in initiation and progression of several cancers, such as lung cancer, hepatocellular carcinoma and laryngeal squamous cell carcinoma. Nevertheless, whether RGMB-AS1 regulates glioma development is not investigated. In this study, we aimed to determine its roles in glioma. METHODS: qRT-PCR and Western blotting were used to measure gene expression. CCK8 and colony formation assays were utilized to analyze proliferation. Transwell assay was used to determine cell migration and invasion. Luciferase reporter assay was used to validate the interactions among RGMB-AS1, miR-1200 and HOXB2. RESULTS: RGMB-AS1 was upregulated in glioma tissues and associated with glioma grade and patients' prognosis. Moreover, RGMB-AS1 silencing significantly inhibited the proliferation, migration and invasion of glioma cells. RGMB-AS1 downregulation led to more tumor cells arrested in the quiescent state. Mechanistically, we found that RGMB-AS1 was a molecular sponge for miR-1200. MiR-1200 level was inhibited by RGMB-AS1. And RGMB-AS1 promoted HOXB2 expression via sponging miR-1200. Restoration of HOXB2 effectively rescued the abilities of proliferation, migration and invasion in RGMB-AS1-depleted glioma cells. CONCLUSION: Collectively, our work clarified that RGMB-AS1/miR-1200/HOXB2 signaling exerts an essential role in regulating glioma progression.

Resident Microglia Activate before Peripheral Monocyte Infiltration and p75NTR Blockade Reduces Microglial Activation and Early Brain Injury after Subarachnoid Hemorrhage.

Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) contributes to high morbidity and mortality. Although it is well recognized that acute neuroinflammation reaction is one of the most important triggers of EBI, pharmacotherapy proved to be clinically effective against the initiating of neuroinflammation after SAH is lacking. The resident microglia and infiltrated peripheral monocyte are two main types of immune cells in central nervous system (CNS) and control the inflammation process in brain after SAH. But the time course and relative contributions of these two immune cell activations after SAH are unknown. The p75 neurotrophin receptor (p75NTR), member of TNF receptor superfamily, expresses on infiltrated peripheral monocytes and suppresses their proinflammatory action after brain insults. But the p75NTR expression on resident microglia in vivo is rarely explored and their function keeps elusive. Therefore, we designed this study to investigate the time course of resident microglia activation and peripheral monocyte infiltration, as well as the microglial expression of p75NTR by using CX3C-chemokine receptor 1 (Cx3cr1) and chemokine receptor 2 (Ccr2) double transgenic mice (Cx3cr1GFP/+Ccr2RFP/+) after SAH. The results showed activated microglia was observed in cortex as early as 24 h and further increased at 48 and 72 h post SAH, while the infiltrated monocyte was not found until 72h. In addition, activated microglia expressed p75NTR acutely and p75NTR specific antagonist TAT-Pep5 significantly reduced microglia activation, neuroinflammation and EBI from 24 to 72 h. Together, these data suggest that the early neuroinflammation reaction might be initiated and intensified mainly by resident microglia rather than infiltrated monocyte at least in the first 48 h after SAH and p75NTR blockading by TAT-Pep5P might alleviate EBI through mediating microglial activation.

Long noncoding RNA gastric cancer-associated transcript 3 plays oncogenic roles in glioma through sponging miR-3127-5p.

Evidence is emerging that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. LncRNA gastric cancer-associated transcript 3 (GACAT3) is reported to participate in the development of breast cancer, colorectal cancer, nonsmall cell lung cancer, and gastric cancer. However, whether it is implicated in glioma has not been elucidated. Here, we found that GACAT3 level was aberrantly elevated in glioma tissues and cell lines. Higher GACAT3 expression predicted lower survival rate. Knockdown of GACAT3 suppressed the proliferation, colony formation, migration, and invasion but promoting apoptosis in glioma cells. Next, we determined that GACAT3 contributes to glioma progression through inhibiting microRNA (miR)-3127-5p. Subsequently, ELAVL1 was identified as a direct target of miR-3127-5p by bioinformatics analysis and luciferase reporter assay. Moreover, we confirmed that GACAT3 promoted ELAVL1 expression through sponging miR-3127-5p, leading to glioma progression. Taken together, our study elucidated that GACAT3/miR-3127-5p/ELAVL1 signaling regulates glioma development and might be a promising therapeutic target.