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.

Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P ＜ 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P ＜0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It suggests that the optimal concentration of sumatriptan significantly down-regulates CGRP over-expression via intracellular ERK1/2 and JNK signaling transduction pathways in TG after organ culture.

Objective To analyze the characteristics of the common first attack of headache in patients with cerebral venous sinus thrombosis (CVST). Methods The clinical data of 51 patients who were diagnosed as CVST with MR venography (MRV)or DSA were collected retrospectively. The patients were divided into either a acute group (≤3 week,n= 32)or a chronic group (>3 weeks, n=19). Results (1)The age of onset of symptoms in these patients was 20 to 40 years,and most of them were females. Of all the first symptoms,headache ranked first,accounting for 84. 3%(43/51 );headache only accounted for 52. 9%(27/51 ),headache with other symptoms (ophthalmic symptoms, hemiplegia,and aphasia,etc. )accounted for 31. 4%(16/51 ),and other symptoms such as epilepsy, paralysis,and ophthalmic symptoms accounted for 15. 7%(8/51). (2)The proportion of headache only as the first symptom in the acute group was higher than that in the chronic group (65. 6% vs. 31. 6%,P<0. 05), and the proportion of chronic headache with other symptoms as the first symptom in the chronic group was higher than that of the acute group (P<0. 05). In addition,the proportion of the first symptom including ophthalmic manifestations in the chronic group was higher than that of the acute group (P <0.01 ). (3)Forty-three patients with headache,dull headache or distensible pain accounted for 72. 1%(31/43), thunderclap headache accounted for 11. 6%(5/43),and other kinds of headache accounted for 16. 3%(6/43),however,there were no significant differences about the types of headache between the two groups (all P>0. 05 ). Conclusion Young patients without previous history of migraine,especially women of childbearing age with sudden onset and progressive worsening headache,and the patients with idiopathic intracranial hypertension,CVST should be considered as an important possibility.

Objective To study the relationship between serum UA level and early outcome in acute ischemic stroke (AIS) patients. Methods Four hundred and twenty-one AIS patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2015 to March 2016 were divided into good outcome group (n = 232) and poor outcome group (n = 189) according to their modified Rankin scale (mRS) score. Their demographic data, risk factors for vascular disease, laboratory testing parameters, imaging and clinical data and NIHSS score were recorded and compared. The relationship between serum UA level and early poor outcome in AIS patients was analyzed by unconditioned logistic regression analysis. Results The incidence of AF and cerebral infarction in the territory of anterior cerebral artey and middle cerebral artery, SBP, serum TC,LDL and urea levels,NIHSS and mRS score, and mortality were significantly higher and the hospital stay time was significantly longer while the serum UA level and GCS score were significantly lower in poor outcome group than in good outcome group (P＜0.05,P＜0.01). Unconditioned logistic regression analysis showed that SBP,NIHSS score and serum UA level were the major risk factors for the early poor outcome in AIS patients (OR = l.017,95％CI:1.003-1.031,P = 0.018;OR = 1.274,95％CI:1.178-1.378,P=0.000;OR=0.993,95％CI:0.989-0.996, P = 0.000). Conclusion The low serum UA level is related with the early poor outcome in AIS patients.