[The pharmacological mechanism of gastrodin on calcitonin gene-related peptide of cultured rat trigeminal ganglion].

The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.

Intracerebral hemorrhage influences hippocampal neurogenesis and neurological function recovery via Notch1 signaling.

Intracerebral hemorrhage (ICH) is associated with high rate of mortality and morbidity, but lacks effective therapies. Accumulating studies indicated that the hippocampal neurogenesis plays an essential role in the recovery of neurological function after ICH. The Notch1 signaling pathway shows important roles in neurogenesis. However, the effects of Notch1 on the recovery of neurological function after ICH remain unclear. Here, we used ICH mice model to investigate whether Notch1 signaling was involved in the hippocampal neurogenesis and the recovery of neurological function post-ICH. Our results showed that the rate of symmetric division pattern of hippocampal neural stem cells (NSCs) decreased significantly at 3 days after ICH. Meanwhile, the expression of Notch1 in the hippocampus also was reduced significantly. However, Notch1 activator treatment enhanced the expression of Notch1 and increased the number of Sox2+GFAP+ cells. Further, the rate of symmetric division pattern of NSCs also increased after Notch1 activator treatment in mice with ICH. Importantly, the number of DCX+ cells and BrdU+NeuN+ in hippocampus were increased on 28 days post-ICH as the Notch1 expression was upregulated. The motor function and spatial memory ability in post-ICH mice following Notch1 activator treatment also were improved. Taken together, our results suggested that Notch1 signaling could influence the recovery of long-term neurological function by regulating the proliferation and differentiation of the hippocampal NSCs in mice after ICH. Our study may provide ideas for the improvement of neurological function and spatial memory defects after ICH.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

OBJECTIVE: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT). METHODS: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated. RESULTS: We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score (p = 0.364) or occur-to-treatment time (p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-ß (p = 0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in the control group. CONCLUSIONS: Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS. CLINICALTRIALSGOV IDENTIFIER: NCT03218293. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.

Association between platelet distribution width and poor outcome of acute ischemic stroke after intravenous thrombolysis.

PURPOSE: The platelet distribution width (PDW) reflects the status of platelet activity and may be useful for early predictions of the clinical outcome of stroke patients. The purpose of the study was to determine the associations between PDW and clinical outcomes after intravenous thrombolysis in stroke patients. PATIENTS AND METHODS: Acute ischemic stroke patients who received intravenous treatment with recombinant tissue-type plasminogen activator were selected for inclusion in the retrospective cohort of this study. The relations between PDW at admission and clinical outcomes were analyzed, including a poor outcome as assessed using the modified Rankin Scale at 3 months, early neurological improvement, and any hemorrhage. The effect of PDW at admission on a poor outcome at 3 months was analyzed using a multivariable logistic regression model with adjustment for potential confounders. The optimal PDW cutoff for predicting poor outcome at 3 months was determined by analyzing the receiver operating characteristics curve. RESULTS: PDW was significantly higher for a good outcome than a poor outcome (p=0.005), with median (interquartile range) values of 16.2 (13.2-17.2) and 13.6 (12.5-15.9), respectively. PDW was also higher in patients with early neurological improvement than in patients without improvement (p=0.020) and did not differ between hemorrhage and nonhemorrhage patients. The association between PDW <16.05% and poor outcome remained in a multivariable logistic regression analysis, with an OR of 6.68 and a 95% CI of 1.69-26.49 (p=0.007). CONCLUSION: Results suggest a novel hypothesis that a lower PDW may be related with a poor outcome at 3 months after intravenous thrombolysis in acute ischemic stroke patients.

De Ritis ratio (AST/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke.

PURPOSE: The aspartate transaminase/alanine transaminase ratio (De Ritis ratio, AAR) was reported to be associated with patients' prognosis in certain diseases recently. The objective of the current study was to determine the association between the AAR at admission and poor outcome at 3 months in acute ischemic stroke (AIS) patients. PATIENTS AND METHODS: This retrospective cohort study included patients who experienced their first-ever AIS between June 2015 and March 2016. The primary outcome measure was a poor outcome at 3 months (modified Rankin Scale score >2). Multivariate logistic regression models were used to assess the relationship between AAR quartiles and clinical outcomes among the AIS patients. Receiver operating characteristic curve analysis was applied to identify the optimal cutoff for AAR in predicting the prognosis of AIS. RESULTS: In terms of the relationship between poor outcome and AAR, the adjusted odds ratio comparing the highest and lowest AAR quartiles was 2.15 (95% confidence interval =1.14-4.05). An AAR of 1.53 was identified as the optimal cutoff. In a prespecified subgroup analysis according to the time from symptom onset to treatment (>24 vs ≤24 hours), there was no significant difference in the effect of AAR >1.53 between the two groups. CONCLUSION: An increased AAR at admission is significantly associated with a poor outcome at 3 months in AIS patients.

Early predictors of hematoma resorption rate in medically treated patients with spontaneous supratentorial hemorrhage.

Spontaneous intracranial hemorrhages are associated with a relatively high mortality rate, and there is no effective treatment so far. Hematoma resorption speed after intracranial hemorrhage (ICH) is believed to correlate with clinical outcome. However, little is known about hematoma resorption rates following spontaneous ICH. The aim of this study is to identify factors that can influence the rate of hematoma resorption in patients with spontaneous supratentorial ICH. We studied 80 patients admitted at the First Affiliated Hospital of Xi'an JiaoTong University from November 2008 to April 2012. The rate of hematoma resorption was calculated for each patient by measuring the variation in the volume of the hematoma (mL) from two computerized tomography brain scans divided by the time factor (days) separating the respective scans. Non-parametric and standard multiple linear regression methods were used for statistical analysis. The size of the hematoma was identified as a predictor of the rate of hematoma resorption. For supratentorial hematomas with a maximum volume of 45 mL, the larger the volume, the greater the rate of resorption. Non-hypertensive patients had a more favorable rate of hematoma resorption than those who were hypertensive. A low serum high-density lipoprotein (HDL) level (<0.83 mmol/L) was associated with a slower hematoma resorption rate. Therefore, a spontaneous ICH hematoma of less than 45 mL, a history of chronic hypertension, and a lower level of HDL were found to be the predictors of the hematoma resorption rate in the first 7-day period following ICH onset.