Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT.

BACKGROUND Ischemia-reperfusion injury is caused by a blood reperfusion injury in ischemic brain tissue, and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. MiR-122 is closely related to ischemia-reperfusion injury in the myocardium, kidney, and liver; however, the role in cerebral ischemia-reperfusion injury has not been established. MATERIAL AND METHODS In this study, cerebral ischemia-reperfusion injury was established in a rat model, and the control group was a sham-operated group. After ischemia-reperfusion injury for 6, 12, and 24 hours, brain tissue specimens were collected and the expression of miR-122 and DJ-1 were determined using quantitative real-time polymerase chain reaction. Flow cytometry was used to determine the reactive oxygen species (ROS) content. The modified Neurological Severity Score (mNSS) scale was used to evaluate the sensory and motor function defects of the rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and enzyme activity were determined. The rats in the cerebral ischemia-reperfusion injury model were divided into 2 groups (antagomir-NC group and antagomir miR-122 group). Brain neuron RN-c cells were divided into the following 4 groups: antagomir-NC, antagomir miR-122, pIRES2-blank, and pIRES2-DJ-1. Seventy-two hours after transfection, ischemia-reperfusion treatment was carried out and conventional cultured RN-c cells were used as the control group. Flow cytometry was used to detect apoptosis and western blot was used to detect the expression of DJ-1, PTEN, AKT, and p-AKT. RESULTS The expression of miR-122 increased significantly in the process of ischemia-reperfusion damage after cerebral infarction, while the expression of DJ-1 decreased significantly. Downregulation of miR-122 significantly increased the expression of DJ-1, enhanced the activity of the PTEN/PI3K/AKT pathway, reduced cell apoptosis, and alleviated cerebral ischemia-reperfusion injury. CONCLUSIONS Inhibition of miR-122 can decrease cerebral ischemia-reperfusion injury by upregulating DJ-1-PTEN/PI3K/AKT pathway.

The Promising Effects of Transplanted Umbilical Cord Mesenchymal Stem Cells on the Treatment in Traumatic Brain Injury.

Many studies have reported the recovery ability of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for neural diseases. In this study, the authors explored the roles of UC-MSCs to treat the traumatic brain injury. Umbilical cord-derived mesenchymal stem cells were isolated from healthy neonatal rat umbilical cord immediately after delivery. The traumatic brain injury (TBI) model was formed by the classical gravity method. The authors detected the behavior changes and measured the levels of inflammatory factors, such as interleukin-lß and tumor necrosis factor-α by enzyme linked immunosorbent assay (ELISA) at 1, 2, 3, 4 weeks after transplantation between TBI treated and untreated with UC-MSCs. Simultaneously, the expression of glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) were measured by real-time-polymerase chain reaction and ELISA.The authors found that the group of transplantation UC-MSCs has a significant improvement than other group treated by phosphate buffered saline. In the behavioral test, the Neurological Severity Scores of UC-MSCs + TBI group were lower than TBI group (P < 0.05), but not obviously higher than control group at 2, 3, and 4week, respectively. The inflammatory factors are significantly reduced comparison with TBI group (P < 0.05), but both GDNF and BDNF were higher than TBI group (P < 0.05). The results indicated that UC-MSCs might play an important role in TBI recovery through inhibiting the release of inflammatory factors and increasing the expression of GDNF and BDNF.

Osthole Upregulates BDNF to Enhance Adult Hippocampal Neurogenesis in APP/PS1 Transgenic Mice.

Adult hippocampal neurogenesis occurs in the dentate gyrus (DG) of the mouse hippocampus, and plays roles in learning and memory progresses. In amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice, a rodent model of Alzheimer's disease (AD), severe impairment of neurogenesis in the dentate subgranular zone (SGZ) of the DG has been reported. Osthole, an active constituent of Cnidium monnieri (L.) CUSSON, has been reported to exert neuroprotective effects and may promote neural stem cell proliferation. However, whether osthole ameliorates spatial memory deficits and improves hippocampal neurogenesis in APP/PS1 mice remains unknown. In this study we found that osthole (30 mg/kg intraperitoneally (i.p.) once daily) treatment dramatically ameliorated the cognitive impairments by Morris Water Maze test and passive avoidance test, and augmented neurogenesis in the DG of hippocampus in APP/PS1 mice. Furthermore, osthole treatment upregulated expression of brain-derived neurotrophic factor (BDNF) and enhanced activation of the BDNF receptor tyrosine receptor kinase B (TrkB) following increased phosphorylation of cyclic AMP response element-binding protein (CREB), indicating that osthole improves neurogenesis via stimulating BDNF/TrkB/CREB signaling in APP/PS1 transgenic mice.

Coinfection of Streptococcus suis and Nocardia asiatica in the human central nervous system: A case report.

BACKGROUND: Streptococcus suis (S. suis) is an anthropozoonotic pathogen that shows clinical manifestations of meningitis, septicemia, and arthritis in infected humans. Nocardia is another type of anthropozoonotic bacteria, with clinical manifestations of skin, lung, and brain abscesses in infected humans. Few intracranial infections caused by S. suis or Nocardia have been reported. To the best of our knowledge, no study has reported a patient with simultaneous intracranial infection by S. suis and Nocardia. CASE SUMMARY: A 66-year-old male presented at Liaocheng People's Hospital (Liaocheng, Shandong Province, China) reporting dizziness with nausea and vomiting. Metagenomic next-generation sequencing (mNGS) was performed on cerebrospinal fluid for examination, and the patient was diagnosed with suppurative meningitis caused by S. suis infection. He received anti-infection treatment with penicillin sodium and ceftriaxone. The patient's condition initially improved but then deteriorated. Further mNGS of cerebrospinal fluid revealed both S. suis and Nocardia. Imaging examination revealed a brain abscess. Furthermore, a mixed infection of S. suis and Nocardia was detected in the patient's central nervous system. The patient was treated with antibiotics and sulfamethoxazole. He was discharged after his condition improved. CONCLUSION: This case shows that the disease can be recurrent in patients with intracranial infection of a rare pathogen. The possibility of mixed infection should also be considered, especially in patients treated with immunosuppressive agents. mNGS of cerebrospinal fluid is a supplement to conventional microbial pathogen identification methods. Patients with unknown pathogen diagnosis, early extensive use of antibiotics and infection with rare pathogens can be diagnosed by the combination of conventional methods and mNGS of cerebrospinal fluid.

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment.

BACKGROUND: The diagnostic value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infectious diseases after empirical treatment has not been reported. AIM: To investigate the diagnostic value of mNGS of cerebrospinal fluid (CSF) in the empirically treated CNS infectious diseases. METHODS: A total of 262 CSF samples from patients with suspected CNS infections were collected between August 2020 and December 2021. Both mNGS and conventional methods were used for testing. The conventional methods included microbial culture, smear, polymerase chain reaction, etc. RESULTS: Among 262 suspected cases, 183 cases (69.84%) were diagnosed as CNS infection, including 86 cases of virus infection (47.00%), 70 cases of bacterial infection (38.25%) and 27 cases of fungal infection (14.76%). The sensitivity and specificity of mNGS were 65.6% (95%CI: 58.2%-72.3%) and 89.6% (95%CI: 79.1%-95.3%), respectively. The PPV of mNGS was 94.5% (95%CI: 88.6%-97.6%), and the NPV was 48.8% (95%CI: 39.7%-57.9%). The pathogen detective sensitivity and accuracy of mNGS were higher than those of conventional methods (Sensitivity: 65.6% vs 37.2%; P < 0.001; Accuracy: 72.0% vs 50%, P < 0.001). The results showed that compared with conventional methods, mNGS technology was a more sensitive method for the diagnosis of CNS infection after empirical treatment. CONCLUSION: mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.

Diagnostic utility of GDF15 in neurodegenerative diseases: A systematic review and meta-analysis.

INTRODUCTION: GDF15 may be a potential biomarker for neurodegenerative diseases. In this analysis, we aimed to quantitative analysis the levels of GDF15 in patients with neurological diseases and in health control, and then to determine its potential diagnostic utility. METHODS: Two researchers separately conducted a systematic search of the relevant studies up to January 2021 in Embase, PubMed, and Web of Science. Effect sizes were estimated to use the standardized mean difference (SMD) with 95% confidence interval (CI). Sensitivity and specificity were calculated by the summary receiver operating characteristics curve (SROC) method. The sensitivity analysis was performed by the "one-in/one-out" approach. Considering the considerable heterogeneity among studies, random-effects model was used for the meta-analysis investigation. RESULTS: A total of eight articles were included in this meta-analysis and systematic review. The pooled results of the random effect model indicated GDF15 levels were significantly higher in patients with neurodegenerative disease than healthy people (SMD = 0.92, 95% CI: 0.44-1.40, Z = 3.75, p < 0.001). Sensitivity and specificity of biomarker of GDF15 were 0.90 (95% CI: 0.75-0.97), 0.77 (95% CI: 0.67-0.65), and AUC = 0.87 (95% CI: 0.84-0.90), respectively. CONCLUSIONS: GDF15 levels were higher in patients with neurodegenerative disease than healthy people. And serum levels of GDF15 were a better marker for diagnostic utility of neurodegenerative disease.

Relationship between white blood cell count at admission and short term outcome in patients with acute cerebral infarction.

PURPOSE: We studied the association between admission white blood cell (WBC) count and short term outcome in patients with acute cerebral infarction. METHODS: 2808 patients with acute cerebral infarction were included in the study. WBC count and other variables were collected within the first 24 hours of admission. Clinical outcomes (death or dependency) were evaluated by neurologists during hospitalization. The associations between WBC count and in-hospital death or dependency at discharge were analyzed using a multiple logistic model. RESULT: Multivariate-adjusted odds ratio (95% confidence intervals) of dependency associated with patients with WBC of 10.0-10.9×109/L, 11.0-11.9×109/L, ≥12.0×109/L were 1.46(0. 87-2. 45), 6.21(3. 70-10. 42) and 7.01(4. 53-10. 87), respectively, when compared with patients with admission WBC counts < 10.0x109/L. Multivariate-adjusted odds ratio (95% confidence intervals) of death associated with WBC 10.0-10.9×109/L, 11.0-11.9×109/L and ≥12.0×109/L were 2.098(0. 96-4. 58), 4.79(2. 24-10. 22) and 5.59(3. 14-9. 98), respectively. CONCLUSION: Increased WBC count at admission was significantly and positively associated with in-hospital death or dependency at discharge among patients with acute cerebral infarction.

Orexin-A exacerbates Alzheimer's disease by inducing mitochondrial impairment.

Alzheimer's disease (AD) is a progressive neurodegenerative disease which is characterized by the accumulation of amyloid-ß peptide (Aß). Orexin-A is a neuropeptide which has been reported to participate in the pathogenesis of AD. Thus, we aimed to investigate the possible mechanism by which Orexin-A acts in AD. APP/PS1 transgenic mice, an animal model of AD, were intracerebroventricularly injected with Orexin-A. Aß-treated SH-SY5Y cells were used as a cell model of AD and treated with Orexin-A. The Morris water maze test, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA), electron microscopy, real-time PCR, and other biochemical assays were conducted. The Morris water maze test showed that Orexin-A aggravated cognitive deficit in APP/PS1 mice. Using thioflavine-S staining and ELISA, we found that Orexin-A promoted Aß accumulation in APP/PS1 mice. By evaluating mitochondrial morphology, cytochrome c oxidase activity, ATP level, mitochondrial DNA copy number, and reactive oxygen species, we found that Orexin-A aggravated mitochondrial impairment in APP/PS1 mice and Aß-treated SH-SY5Y cells. Our results indicate that Orexin-A exacerbates AD by inducing mitochondrial impairment. This is a new mechanism that explains how Orexin-A participates in the pathogenesis of AD.

Effects of different anesthesia methods on cognitive dysfunction after hip replacement operation in elder patients.

There are many risk factors for the cause of postoperative cognitive dysfunction (POCD), however, the anesthesia selection always trigger controversy for the POCD occurrence. This study aims to explore the relationship between the anesthesia and the occurrence of POCD in elder patients, and also investigate the mechanism of the POCD. One hundred elder patients with hip replacement were included in this study, which were divided into general anesthesia (GA) and epidural analgesia (EA) group. Minimum mental state examination (MMSE) method was employed to assess the nervous and mental function (POCD) in both analgesia group patients. Aß and tau protein levels in blood were detected by using the ELISA assay. The correlation between MMSE in POCD patients and Aß or tau was analyzed by employing the Spearman rank correlation method. The results indicated that epidural analgesia decreases the MMSE scoring compared to general analgesia (P < 0.05). General analgesia enhanced the Aß and tau level compared to epidural analgesia (P < 0.05). Aß and tau level were increased in the patients with POCD. The POCD occurrence rate in GA group was significantly higher compared to EA group (P < 0.05). MMSE scores of POCD patients positively correlated with Aß or tau level (P < 0.05). In conclusion, the epidural analgesia method was better than general analgesia method for the hip replacement in elder patients. The mechanism of the POCD may be caused by the enhancement of Aß and Tau protein.

Baicalein ameliorated the upregulation of striatal glutamatergic transmission in the mice model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by a loss of projecting dopaminergic neurons in the substantia nigra and diminished dopamine level in the striatum. Dopaminergic deficit consequently leads to the alterations of striatal basal glutamatergic synaptic transmission and plasticity in the medium spiny neurons. The cytokines and neurotoxins released from the reactive immune cells induced the loss of the projecting dopaminergic neurons in the substantia nigra, which triggering the pathogenesis of PD. The present study investigated the effect of treatment with baicalein (5,6,7-trihydroxyflavone) on the central cytokine synthesis, striatal glutamatergic transmission, and behavioral performance in the rotarod task in the mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with baicalein significantly attenuated the upregulation of striatal basal glutamatergic strength by decreasing the presynaptic glutamate release and recovering the insertion of postsynaptic glutamate receptor subunit GluR1 induced by MPTP. It also significantly improved the behavioral performance in the rotarod task in the mice injected with MPTP. Treatment with baicalein decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1ß) in the substantia nigra and striatum in the mice injected with MPTP. These results indicated that baicalein might serve as novel approach for the treatment of the patients with PD.

[Risk factors on the recurrence of ischemic stroke and the establishment of a Cox's regression model].

OBJECTIVE: To investigate the risk factors and establish the Cox's regression model on the recurrence of ischemic stroke. METHODS: We retrospectively reviewed consecutive patients with ischemic stroke admitted to the Neurology Department of the Hebei United University Affiliated Hospital between January 1, 2008 and December 31, 2009. Cases had been followed since the onset of ischemic stroke. The follow-up program was finished in June 30, 2010. Kaplan-Meier methods were used to describe the recurrence rate. Monovariant and multivariate Cox's proportional hazard regression model were used to analyze the risk factors associated to the episodes of recurrence. And then, a recurrence model was set up. RESULTS: During the period of follow-up program, 79 cases were relapsed, with the recurrence rates as 12.75% in one year and 18.87% in two years. Monovariant and multivariate Cox's proportional hazard regression model showed that the independent risk factors that were associated with the recurrence appeared to be age (X1) (RR = 1.025, 95%CI: 1.003 - 1.048), history of hypertension (X2) (RR = 1.976, 95%CI: 1.014 - 3.851), history of family strokes (X3) (RR = 2.647, 95%CI: 1.175 - 5.961), total cholesterol amount (X4) (RR = 1.485, 95%CI: 1.214 - 1.817), ESRS total scores (X5) (RR = 1.327, 95%CI: 1.057 - 1.666) and progression of the disease (X6) (RR = 1.889, 95%CI: 1.123 - 3.178). Personal prognosis index (PI) of the recurrence model was as follows: PI = 0.025X1 + 0.681X2 + 0.973X3 + 0.395X4 + 0.283X5 + 0.636X6. The smaller the personal prognosis index was, the lower the recurrence risk appeared, while the bigger the personal prognosis index was, the higher the recurrence risk appeared. CONCLUSION: Age, history of hypertension, total cholesterol amount, total scores of ESRS, together with the disease progression were the independent risk factors associated with the recurrence episodes of ischemic stroke. Both recurrence model and the personal prognosis index equation were successful constructed.