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.

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.

Acute myocardial ischemia (AMI) was induced by occlusion of the left anterior descending (LAD) coronary artery in rats.AMI rats and normal rats were administered with protocatechuic aldehyde(Pal) at a single dose of 20 mg/kg through peritoneal injection.Concentrations of Pal,protocatechuic acid (PAC) and vanillic acid (VAC) in plasma were determined by HPLC to evaluate the effect of AMI on pharmacokinetics of Pal in rats.Pal was quickly metabolized to PAC,which was then methylated into VAC.Compared to the normal group,AUC_(0-∞) of PAC significantly increased from 14.01 ±3.11 to 22.31 ±4.96 μg·h/mL in AMI group (P ＜ 0.01),and AUC_(0-∞) of VAC markedly elevated from 19.64 ±4.36 to 38.76±5.75 μg·h/mL (P＜0.01).Both MRT of PAC and VAC increased (0.43 ± 0.08 h vs 0.27 ± 0.04 h,0.61 ± 0.11 h vs 0.38 ± 0.05 h,P ＜ 0.01).Metabolic ratio M/P of PAC increased from 1.43 ±0.31 to 1.77 ±0.22 (P ＜0.05).Results indicated that AMI status had great influence on pharmacokinetic behavior of Pal.Meanwhile,the level of methylation was greatly increased.

Objective:To investigate the efficacy and feasibility of mechanical thrombectomy (MT) via carotid artery salvage puncture in patients with acute anterior circulation large vessel occlusive stroke. Methods:A retrospective analysis was performed. Eight patients with acute anterior circulation large vessel occlusive stroke underwent MT via carotid artery salvage puncture in Departments of Neurology, First People's Hospital of Xianyang, Xi'an Ninth Hospital, Xi'an Daxing Hospital and XD Group Hospital from June 2021 to September 2023 were enrolled. Occlusion location, time from onset to femoral artery puncture, causes of carotid artery salvage puncture, time from femoral artery puncture to carotid artery salvage puncture, time from successful carotid artery puncture to vascular recanalization, modified thrombolysis in cerebral infarction (mTICI) score immediately after MT, and scores of National Institutes of Health Stroke Scale (NIHSS) 24 h after MT and modified Rankin Scale (mRS) 90 d after MT were analyzed. Results:Of the 8 patients, 7 had M1 segment occlusion and 1 patient had M2 segment occlusion. Direct thrombectomy was not possible resulting from type III aortic arch in 3 patients, aortic arch replacement in 1 patient, right common carotid artery twisting angle in 1 patient, left common carotid artery twisting angle in 2 patients, and bilateral femoral artery occlusion in 1 patient. All 8 patients had successful carotid artery puncture under local anesthesia, including 7 with mTICI 3 and 1 patient with mTICI 2b. Average time from successful carotid artery puncture to vascular recanalization was about 35 min, ranged 10-90 min. All patients had decreased NIHSS score 24 h after MT compared with before MT, and no complications such as hematoma or airway compression occurred in carotid artery puncture site. Six patients had mRS scores of 0-2 and 2 had scores of 6 (death cause: pulmonary infection) 90 d after surgery.Conclusion:For patients with patients with acute anterior circulation large vessel occlusive stroke, MT via carotid artery salvage puncture is a safe and feasible method in cases of difficulty in establishing thrombectomy route via femoral artery such as type III aortic arch, common carotid artery twisting angle, abdominal aorta occlusion.