针刺治疗脑缺血再灌注损伤：与减轻炎症反应有关？

摘要 背景：脑缺血己成为严重影响人类健康的主要疾病之一。针刺治疗急性脑缺血的疗效是公认的但其治疗机制不明。目的：探讨脑缺血状态下核转录因子-kB（NF-kB）、细胞间黏附分子-1 (ICAM-1)、血管细胞黏附分子-1（VCAM-1）的变化及针刺的干预作用。 设计及时间：分子生物学实验于2008年12月至2009年10月在中南大学湘雅医院神经外科实验室完成。 研究对象/材料/对象：健康SD大鼠46只随机分成假手术组、脑缺血组、针刺预处理组,针刺干预组。方法：以线栓法制作大鼠大脑中动脉缺血2h再灌注模型,并用针刺干预,然后应用RT-PCR逆转录反应、蛋白免疫印迹法分析观察各组大鼠脑组织NF-kB ,ICAM-1、VCAM-1 mRNA及蛋白的表达。结果：脑缺血大鼠动物模型被成功复制,其神经功能评分表明,针刺明显改善上述指标,尤其对再灌注70h组的影响显著;针刺组脑缺血再灌注后NF-kB、ICAM-1、 VCAM-1mRNA及蛋白质的表达明显下降。结论：针刺可明显改善脑缺血再灌注后的神经功能评分指标,并且该作用可能与抑制脑缺血再灌注后NF-kB、ICAM-1、VCAM-1的表达,下调脑缺血区域组织的NF-kB、ICAM-1、VCAM-1 mRNA及蛋白质表达水平有关。     

褪黑素对大鼠脑缺血时白细胞浸润和 ICAM-1表达的影响

目的研究褪黑素(melatonin,MT)对大鼠脑缺血损伤缺血区髓过氧化物酶(myeloperoxidase,MPO)的活性及细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达的影响。方法线栓法造成大鼠大脑中动脉栓塞制成脑缺血模型,手术分为正常对照组、缺血组、MT治疗组,MT治疗组缺血前30min给予MT (20mg/kg)腹腔注射。术后在相应时间点取缺血侧脑组织,用分光光度计检测MPO的活性,用免疫组化检测I- CAM-1蛋白的表达。结果与正常对照组比较,缺血组各时间点MPO的活性及ICAM-1蛋白的表达均升高,而与缺血组比较MT治疗组各时间点MPO的活性及ICAM-1蛋白的表达均降低。结论MT可能能通过降低MPO的活性即抑制白细胞的浸润和降低ICAM-1蛋白的表达,对缺血的脑组织产生保护作用。     

缺氧诱导因子-1α、ICAM-1、γ-干扰素及BDNF在脑出血模型大鼠中的表达水平变化

目的 探讨缺氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)、细胞间黏附分子-1(Intercellular cell adhesion molecule-1,ICAM-1)、γ-干扰素(Interferon-γ,IFN-γ)及脑源性神经营养因子(Brain derived neurotrophic factor,BDNF)在脑出血模型大鼠中的表达水平变化。方法 选取30只SD健康雄性大鼠,其中10只大鼠作为正常组,不做任何处理,另外20只大鼠建立脑出血模型,使用Morris水迷宫对2组大鼠学习记忆能力进行测试,取大鼠脑组织制作标本待检。酶联免疫吸附试验法检测HIF-1α、ICAM-1、IFN-γ及BDNF水平,Western blot检测磷酸化蛋白激酶(p-AKT)、Bax蛋白和B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)蛋白表达水平。结果 脑出血模型大鼠主要表现为肢体瘫痪,有追尾现象出现,大鼠不能正常站立或打滚,不能进行自发性活动,出现意识障碍; 脑出血组大鼠逃避潜伏期长于正常组,穿越平台次数少于正常组(P<0.05); 脑出血组大鼠HIF-1α、ICAM-1、IFN-γ水平高于正常组大鼠,且第14 d脑出血组HIF-1α、ICAM-1、IFN-γ水平低于第7 d(P<0.05); 脑出血组大鼠BDNF水平低于正常组,第14 d脑出血组BDNF水平高于第7 d(P<0.05); 脑出血组大鼠p-AKT、Bcl-2水平均高于正常组,Bax水平低于正常组(P<0.05)。结论 HIF-1α、ICAM-1、IFN-γ及BDNF在大鼠脑出血中均呈现异常表达。     

Celecoxib对糖尿病大鼠缺血再灌注脑组织NF-kB和ICAM-1表达的影响

目的探讨celecoxib对糖尿病大鼠脑缺血再灌注后脑组织中NF-xB和ICAM-1表达的影响。方法采用SD大鼠腹腔注射链脲佐菌素（STZ）和线栓法制作糖尿病大鼠大脑中动脉缺血再灌注模型;大鼠分为假手术组（S组）、脑缺血再灌注生理盐水组（NS组）、celecoxib低剂量组（LCIR组）和高剂量组（HCIR组）,分别于缺血后30rain给予生理盐水或celecoxib溶液灌胃,再灌注后6、12、24、48h将大鼠断头取脑,免疫组化法检测脑组织中NF-kB和ICAM-1的表达水平。并对大鼠进行神经功能缺损评分。结果NS组、LCIR组、HCIR组大鼠神经功能缺损评分有显著差异（P〈0．05）;NS组、LCIR组、HCIR组NF-kB阳性细胞及ICAM-1阳性微血管主要表达于缺血周边区,较S组表达明显增强（P〈0．05）,LCIR组、HCIR组NF_KB阳性细胞表达率及ICAM-1阳性微血管数较NS组减少（P〈0．05）,LCIR组、HCIR组之间未见明显差异（P〉0．05）,每组不同时间点之间NF-gB阳性细胞表达率有明显差异（P〈0．05）以及它们之间的ICAM-1阳性微血管数也有明显差异（P〈0．05）。结论celecoxib可能通过抑制糖尿病大鼠脑缺血一再灌注后脑组织中NF-kB和ICAM-1的表达而减轻神经功能缺损,从而发挥脑保护作用。     

白介素-10对脑出血大鼠脑组织核因子-кB、细胞间黏附分子-1表达及神经细胞凋亡的影响

目的探讨白介素(IL)-10对脑出血大鼠脑组织核因子(NF)-кB、细胞间黏附分子(ICAM)-1表达及神经细胞凋亡的影响。方法 96只SD大鼠随机分为正常组、对照组、IL-10低剂量组和高剂量组,后3组再随机分为6 h、12 h、1 d、3 d及7 d 5个时间点。应用Ⅶ型胶原酶注射法制备脑出血模型;制模成功后3 hIL-10低剂量组和高剂量组分别给予IL-10 5μg/kg或30μg/kg、对照组给予生理盐水腹腔注射,以后每天1次。应用免疫组化法测定各组血肿周围脑组织NF-кB及ICAM-1表达,原位末端标记法检测脑组织细胞凋亡。结果与正常组比较,其他各组各时间点脑组织NF-кB、ICAM-1表达明显升高,神经细胞凋亡数量明显增多(均P<0.01)。与对照组比较,IL-10低剂量组NF-кB表达制模后12 h开始降低,ICAM-1表达及神经细胞凋亡数量自1 d开始降低,7 d时降低最显著(P<0.05～0.01);IL-10高剂量组上述变化在制模后12 h开始,且下降程度更显著(P<0.05～0.01)。结论 IL-10可抑制脑组织NF-кB及ICAM-1表达,减轻血肿周边炎症反应及神经细胞凋亡,对出血性脑损伤起保护作用;高剂量组作用更明显。     

罗格列酮对硝酸甘油诱导偏头痛大鼠的保护作用

目的观察罗格列酮对硝酸甘油诱导大鼠偏头痛模型的保护作用。方法 48只雄性SD大鼠随机分为模型组、罗格列酮组和对照组。模型组(按Tassorelli法皮下注射硝酸甘油复制大鼠偏头痛模型),罗格列酮组(于造模后30 min腹腔注射罗格列酮),对照组(不造模,皮下注射生理盐水)。观察大鼠行为学变化,采用免疫组化和Western blot法观察三叉神经颈复合体过氧化物酶体增殖物激活受体γ(PPARγ)及白介素-6(IL-6)、细胞间黏附分子-1(ICAM-1)、基质金属蛋白酶-9(MMP-9)表达。结果对照组三叉神经颈复合体中PPARγ为弱阳性表达,模型组为阳性表达,罗格列酮组为强阳性表达。模型组IL-6、ICAM-1和MMP-9表达高于对照组(P0.05)。罗格列酮组大鼠耳发红、肢频繁挠头、爬笼次数增多、烦躁不安等症状减轻,IL-6、ICAM-1、MMP-9表达较模型组明显下降(P0.05)。结论偏头痛时PPARγ表达增强;罗格列酮可通过活化PPARγ,下调IL-6、ICAM-1、MMP-9对偏头痛具有一定的保护作用。     

原花青素对D-半乳糖致衰老大鼠小脑组织中IL-6和TNF-α水平的影响

目的探讨原花青素(PC)对D-半乳糖致衰老大鼠小脑组织中白介素-6(IL-6)、肿瘤坏死因子-(TNF-α)水平的影响。方法 50只健康6月龄雄性Wistar大鼠随机均分为阴性对照组、衰老模型组、维生素E(VE)组、PC 160mg/kg组和80mg/kg组,每组10只,分别给予相应处理后,采用ELISA测定各组大鼠小脑组织中IL-6、TNF-α水平。结果 VE组、PC160mg/kg组和80mg/kg组IL-6、TNF-α水平均低于衰老模型组(P0.05);PC 160mg/kg组与VE组的IL-6、TNF-α水平比较差异无统计学意义(均P0.05);PC 80mg/kg组SOD、GSH-Px水平高于VE组、PC 160mg/kg组(P0.05)。结论PC可能通过改善免疫功能而延缓大鼠小脑组织的衰老。     

α2-去甲基肾上腺素能受体对异丙酚麻醉下大鼠SEP的调节

目的探讨大鼠异丙酚麻醉中α2-去甲基肾上腺素能(NA)受体调节剂对皮层躯体感觉诱发电位(SEP) N20波的影响.方法将SD雄性大鼠30只随机分为3组.单纯异丙酚A组:微量泵以异丙酚10 mg/kg/h、60mg/kg/h的速度依次各静注45 min,停止静注异丙酚直至动物清醒.B组和C组在输注异丙酚的同时腹腔内分别注射可乐定和育亨宾各0.5 mg/kg.分别监测麻醉前、中及苏醒期的皮层SEP N20波的潜伏期和波幅.结果与基础值相比,3组药物对SEP N20波潜伏期均无显著影响;A组对SEP N20波的波幅无影响, B组降低SEP N20波的波幅, C组则增加了SEP N20波的波幅.结论异丙酚麻醉下α2-NA受体激动剂和抑制剂所引起SEP N20波波幅变化可能与镇痛机制有关.     

阿托伐他汀对EAE大鼠脊髓ICAM-1和TGF-β1表达的影响

目的 探讨阿托伐他汀对实验性自身免疫性脑脊髓炎(EAE)大鼠脊髓细胞间黏附分子-1(ICAM-1)和转化生长因子-β1(TGF-β1)表达的影响. 方法 80只清洁级健康雌性Wistar大鼠按照随机数字表法分为4组:正常对照组、EAE模型组、低剂量治疗组、高剂量治疗组,每组20只.各组再分为第14天、21天两个亚组,每个亚组10只.利用新鲜豚鼠全脊髓匀浆及完全福氏佐剂免疫Wistar大鼠建立EAE模型.低、高剂量治疗组大鼠分别给予2 mg/(kg·d)、10 mg/(kg·d)阿托伐他汀灌胃,正常对照组及EAE模型组应用生理盐水灌胃.观察每组大鼠发病情况并进行神经功能障碍评分,采用HE染色方法观察病理改变,免疫组化方法检测ICAM-1及TGF-β1的表达. 结果 与EAE模型组及低剂量治疗组比较,阿托伐他汀高剂量治疗组发病率明显减轻,炎性病灶明显减少,组织中ICAM-1表达明显减少,TGF-β1表达明显增多,差异均有统计学意义(P＜0.05).结论 阿托伐他汀可改善EAE大鼠的临床症状及病理改变,并且与剂量有关,其作用推测与减少ICAM-1表达、提高TGF-β1表达有关.     

大蒜素对全脑缺血再灌注损伤大鼠海马凋亡相关蛋白表达的影响

目的观察大蒜素对全脑缺血再灌注损伤大鼠海马凋亡相关蛋白表达的影响,进一步探讨大蒜素的脑保护机制。方法雄性Wistar大鼠30只,随机分为5组:假手术组(Sham组);缺血再灌注组(IR组);缺血再灌注+大蒜素10 mg/kg(All-10 mg)、20 mg/kg(All-20 mg)、30 mg/kg(All-30 mg)组,夹闭两侧颈总动脉8 min再灌注24 h建立大鼠全脑缺血再灌注模型,取海马组织硫堇染色观察海马组织学改变及存活神经元密度;免疫组织化学染色测定海马CA1区Bcl-2、Bax蛋白的表达。结果与Sham组相比,IR组海马CA1区神经元密度明显降低,Bax蛋白表达明显增加(均P0.05);与IR组相比,大蒜素处理各组海马CA1区神经元密度明显增多,Bcl-2蛋白表达明显增加,Bax蛋白表达明显减少,其中以All-20 mg组变化最显著(均P0.05)。结论大蒜素可以通过影响凋亡相关蛋白的表达而抑制细胞凋亡,从而发挥脑保护作用。     

Vasoactive Intestinal peptide modulates c‐Fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats

Neurogenic inflammation in the dura mater caused by trigeminal nociceptive activation has been implicated in the pathophysiology of migraine. Vasoactive intestinal polypeptide (VIP) is a powerful neuroprotective neuropeptide that can modulate mast cell behavior. Migraine is also associated with sympathetic insufficiency. This study investigates the effects of VIP on the number of mast cells in the dura mater and on c‐Fos expression in the trigeminal nucleus of sympathectomized rats. Experiments were carried out with 32 Sprague‐Dawley male rats with body weights of 200–250 g. In the sympathectomized group, the left superior cervical sympathetic ganglion was removed. In the sympathectomized + VIP group, postoperative VIP 25 ng/kg/day (0.2 ml) was administered for 5 days. In the sham group, the ganglion and nerves were exposed but not dissected. Dura maters were stained with toluidine blue, and brainstems were labeled by indirect immunohistochemistry for c‐Fos. Sympathectomy significantly increased the number of mast cells in both the ipsilateral and the contralateral dura mater (P < 0.001). VIP decreased the number of mast cells in both sides of the dura mater in sympathectomized rats. VIP also decreased c‐Fos expression in the ipsilateral trigeminal nucleus of sympathectomized rats (P < 0.001). In the context of an experimental superior cervical ganglionectomy model of migraine, VIP is an efficient modulator of neurogenic inflammation of the dura. © 2014 Wiley Periodicals, Inc.     

Concomitant upregulation of nuclear factor-kB activity, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma in a rat model

BACKGROUND: Nuclear factor kappa B (NF-kB), proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) are frequently upregulated in the injured brain after traumatic brain injury (TBI). However, the temporal pattern of upregulation is not well defined. AIMS: The current study was undertaken to investigate the temporal profile of the expression of NF-kB, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma of the rat brain. SETTINGS AND DESIGN: A rat model of cortical contusion was produced by a free-falling weight on the exposed dura of right parietal lobe. The rats were randomly divided into control group and TBI groups at hours 3, 12, 24 and 72, and on day 7. MATERIAL AND METHODS: NF-kB binding activity in the surrounding brain of injured area was studied by electrophoretic mobility shift assay (EMSA). The levels of TNF-alpha and IL-6 were detected using ELISA and ICAM-1 expression studied by immunohistochemistry. STATISTICAL ANALYSIS: The data were analyzed by one-way ANOVA followed by Student-Newman-Keuls post hoc test. Relation between variables was analyzed using bivariate correlation with two-tailed test. RESULTS: Compared with that of control group, NF-kB binding activity in the injured brain was significantly increased through 12 h and 7 days postinjury, with the maximum at 72 h. The concentrations of TNF-alpha and IL-6 in the injured brain were significantly increased from 3 h to 7 days and maximal at 24 h postinjury. The number of ICAM-1 immunostained microvessels was significantly increased in the injured brain from 24 h to 7 days postinjury, with its peak at 72 h. Concomitant upregulation of TNF-alpha, IL-6, ICAM-1 and the cytokine mediators NF-kB in the injured brain was observed in the injured brain after cortical contusion, and there was a highly positive relation among these variables. CONCLUSIONS: Cortical contusion trauma could induce a concomitant and persistent upregulation of NF-kB binding activity, TNF-alpha, IL-6 and ICAM-1 in the injured rat brain which might play a central role in the injury-induced immune response of brain.     

Effects of sumatriptan on nitric oxide and superoxide balance during glyceryl trinitrate infusion in the rat. Implications for antimigraine mechanisms

Infusion of glyceryl trinitrate (GTN) into patients with migraine precipitates the onset of a migraine attack several hours after completion of the infusion. Using an infusion of GTN into anaesthetised rats, this study investigates the relationship of regional cerebral blood flux rCBF(ldf), cortical nitric oxide (NO) and cortical superoxide concentrations and the effect of sumatriptan on each variable. In saline treated animals, a 30 min infusion of GTN (2 microgram kg(-1) min(-1), i.v.) was found to markedly increase cortical rCBF(ldf) (133+/-3% of baseline) and NO concentrations (141+/-13% of baseline). Superoxide levels exhibited an inverse relationship to NO levels, decreasing below basal to 48+/-14% of baseline. It is hypothesised that high NO levels during GTN infusion may decrease the detectable superoxide due to "leeching" of the superoxide into low level peroxynitrite formation. In the presence of sumatriptan, a decrease below baseline in cortical rCBF(ldf) (82+/-5% of baseline) and NO concentration (64+/-13% of baseline) was observed throughout GTN infusion, although superoxide levels significantly increased above baseline by 105+/-14 nM (p<0.05, ANOVA post hoc LSD test). The mechanism for this action of sumatriptan is unknown but may include; modulation of cell redox state, NO scavenging or direct manipulation of superoxide release.     

偏头痛大鼠硬脑膜肥大细胞脱颗粒与神经源性炎症相关因子的变化

目的 观察偏头痛大鼠硬脑膜肥大细胞脱颗粒与神经源性炎症相关因子的变化,探讨偏头痛疼痛产生的可能机制.方法 64只SD大鼠随机分为刺激组(32只)和假手术组(32只).电刺激大鼠单侧三叉神经节建立偏头痛模型,放射免疫法测定刺激侧颈静脉血中降钙素基因相关肽(CGRP)的含量.酶联免疫吸附法测定刺激侧颈静脉血中组胺和硬脑膜中前列腺素E2(PGE2)的含量,甲苯胺蓝染色观察硬脑膜肥大细胞的数量及脱颗粒百分率,免疫组织化学染色法、免疫蛋白质印迹技术观察硬脑膜中环氧化酶-2(COX-2)的阳性细胞数及蛋白表达.结果 假手术组和刺激组颈静脉血中CGRP含量分别为(59.20±11.66)pg/ml和(82.84±16.24)pg/ml(t=-3.34);组胺含量分别为(9.87±0.88)ng/ml和(11.59±1.20)ng/ml(t=-3.27);硬脑膜中肥大细胞数量分别为15.46±2.40和11.63±1.67(t=3.71),脱颗粒百分率分别为14.09%±4.53%、29.10%±9.39%(t=-4.07).两组硬脑膜中PGE2的含量分别为(80.70±10.60)pg/ml和(382.30±20.90)pg/ml(t=-16.674);硬脑膜中COX-2阳性细胞数分别为42.00±18.40和139.00±20.50(t=-7.994),COX-2蛋白表达(吸光度值)分别为19.50±9.20和359.20±21.90(t=-5.190).两组间比较,上述指标差异均有统计学意义(P＜0.05).结论 电刺激单侧三叉神经节可诱导硬脑膜肥大细胞脱颗粒及神经源性炎症的产生,相关炎症因子的改变可能是偏头痛疼痛发生的重要病理生理基础.     

Plasma Protein Extravasation Induced in the Rat Dura Mater by Stimulation of the Parasympathetic Sphenopalatine Ganglion

It has been proposed that migraine could result from a neurogenic inflammation of the dura mater. According to this theory, inflammation could be initiated by an axon reflex of nociceptive nerve fibers, but the trigger of this axon reflex remains poorly understood. Previous works have shown that parasympathetic agonists can activate mast cells and/or sensory C-fibers, inducing pain and inflammation. The aim of the present work was to determine whether the activation of intracranial parasympathetic nerve fibers could trigger an inflammatory mechanism within the rat dura mater. Activation of the intracranial parasympathetic system was achieved by electrical stimulation of the sphenopalatine ganglion (SPG). The development of a neurogenic inflammation was estimated either by microscopic examination or by quantitative measurement of plasma protein extravasation (PPE) in the dura. To determine the respective roles of the parasympathetic and sensory innervations, two groups of rats were pretreated either with atropine or with capsaicin. Stimulation of the SPG induced a PPE increase of about 200% in the stimulated side on the dura mater. Extravasated material was mainly concentrated around small blood vessels. This extravasation was significantly reduced by capsaicin pretreatment and completely abolished by atropine. Infusion of carbachol in the common carotid artery induced PPE in the ipsilateral dura comparable to that induced by electrical stimulation of the SPG. This extravasation was also blocked by atropine infusion. These data indicate for the first time that the parasympathetic nervous system can trigger a neurogenic inflammation in the dura via muscarinic cholinergic receptors. Sensory C-fibers seem to play a role in this phenomenon. With respect to the potential autonomic imbalance described in the etiology of various types of vascular headaches, such a mechanism could be important in inducing attacks.     

Prednisolone reduces nitric oxide-induced migraine

Background and purpose Glyceryl trinitrate (GTN) induces delayed migraine attacks in migraine patients. The purpose of this study was to investigate whether pre‐treatment with prednisolon could decrease this effect of GTN. Methods In this double‐blind, randomized and placebo‐controlled, crossover study 15 migraineurs with migraine without aura were pre‐treated with 150 mg of prednisolone or placebo followed by a 20‐min infusion of GTN (0.5 ug/kg/min). One hour after the GTN‐infusion, the participants were sent home, but continued to rate headache and possible associated symptoms by filling out a headache diary every hour for 12 h. There were two equal primary efficacy end‐points: frequency of delayed migraine and intensity of delayed headache. Results Nine patients experienced a GTN headache fulfilling the diagnostic criteria for migraine without aura on the placebo day compared with four patients on the prednisolone day (P = 0.14). Prednisolone pre‐treatment did not alter the summed or peak immediate headache responses to GTN significantly (P = 0.08, P = 0.07), whereas the peak headache scores during the following 12 h were significantly lower after prednisolone pre‐treatment (median peak score = 1, range 0–8) compared with placebo (median = 4, range 0–8) (P < 0.01). There was no difference between the two treatment days in the effect of GTN on blood flow velocity of the middle cerebral artery (a decrease) or on the dilation of the superficial temporal artery or the radial artery. Conclusion Pre‐treatment with prednisolone did not reduce the immediate GTN‐induced headache, did not inhibit the frequency of delayed headache but significantly decreased the intensity of delayed GTN‐induced headache. These findings suggest that GTN causes induction of inflammatory mediators, and that this is the mechanism of delayed GTN‐induced migraine. They also support a role of inflammatory mediators in spontaneous migraine attacks.     

5-HT7 Receptors Are Involved in Neurogenic Dural Vasodilatation in an Experimental Model of Migraine

Neurogenic dural vasodilation has been demonstrated to play an important role in migraine. 5-HT₇ receptors have been found on trigeminal nerve endings and middle meningeal arteries and demonstrated involved in the dilatation of meningeal arteries. The aim of the present study was to demonstrate whether 5-HT₇ receptors are involved in neurogenic dural vasodilation in migraine. The neurogenic dural vasodilation model of migraine was used in this study. Unilateral electrical stimulation of dura mater was performed in anesthetized male Sprague–Dawley rats. Animals were pretreated with selective 5-HT₇ receptor agonist AS19, 5-HT₇ receptor antagonist SB269970, 5-HT_1B/1D receptor agonist sumatriptan, or vehicles. Blood flow of the middle meningeal artery (MMA) was measured by a laser Doppler flowmetry. AS19 significantly increased the basal and stimulated blood flows of the middle meningeal artery following electrical stimulation of dura mater, and its effect was dose dependent at the early stage. SB269970 and sumatriptan significantly reduced the basal and stimulated blood flows of middle meningeal artery. The present study demonstrates for the first time that 5-HT₇ receptors are involved in neurogenic dural vasodilation evoked by electrical stimulation of dura mater and maybe of relevance in the pathophysiology and treatment of migraine.