Efficacy and Effect of SI17 Therapy on Pancreatic Polypeptide in Vascular and Tension-Type Headache

Background and purpose: Vascular and tension-type headache is most commonly encountered, and SI17 therapy has been tested to treat headache with good results. The efficacy of SI17 therapy for vascular and tension-type headache was compared and the effect of SI17 therapy on pancreatic polypeptide (PP) was studied. Materials and methods: 29 cases of vascular headache (20 cases in acute attack during the trial) and 27 cases of tension-type headache (19 cases in acute attack) were enrolled in the study. Plasma PP level before and 4th day after treatment was measured by radioimmunoassay. Results: SI17 therapy is better for the treatment of vascular headache. Vascular headache with higher PP level and tension-type headache with normal PP level had good therapeutic results. Conclusion: The clinical efficacy is better for vascular headache with the increase of vagus tension and for tension-type headache with normal vagus tension.

Ultrasound-Guided Greater Occipital Nerve Hydrodissection for Treatment of Cervicogenic Headache: A Case Report

We describe an innovative technique of ultrasound-guided greater occipital nerve (GON) hydrodissection for treatment of cervicogenic headache and occipital neuralgia. A 35-year-old female presented to the pain clinic with severe chronic cervicogenic headache impacting her sleep, work and activities of daily living. Conservative management had failed to adequately resolve her pain. Ultrasound-guided suboccipital hydrodissection of the greater occipital nerve was performed with the patient in the prone position. After skin sterilization, the linear ultrasound transducer was oriented in a transverse orientation at the level of the C2-C3 vertebrae. The needle was advanced from medial to lateral “in-plane” under direct ultrasound visualization, until the needle was positioned at the C2 lamina. After confirming the needle tip position, 10 ml of hydrodissection fluid was injected with good visualization of distribution of the solution. The patient described immediate and significant improvement in her symptoms. She reported a sustained decrease in pain scores when followed up in the pain clinic at six and twelve weeks respectively. To the best of our knowledge this is the first application of ultrasound-guided hydrodissection of the GON for cervicogenic headache. It offers a novel, safe and effective technique to aid in the diagnosis and treatment of a common pain condition.

Expert Consensus on the Clinical Application of Tianma Xingnao Capsule in the Treatment of Vascular Cognitive Impairment and Neuropathic Headache

The prescription of Tianma Xingnao Capsule is composed of Gastrodiae Rhizoma,Pheretima,Acori Tatarinowii Rhizoma,Polygalae Radix,Rehmanniae Radix Praeparata,and Cistanches Herba.It has effects of nourishing liver and kidney,dredging collaterals and relieving pain.More than 20 years of clinical application and evidence-based medical research have shown that Tianma Xingnao Capsule has a significant therapeutic effect on vascular cognitive impairment and neuropathic headache.In order to further guide the proper clinical use of this prescription,the consensus expert group conducted a comprehensive analysis of the prescription of Tianma Xingnao Capsule.Combining the existing evidence-based medicine evidence and the experience of clinical experts,this consensus report standardized the usage,dosage,duration and safety of Tianma Xingnao Capsule in the treatment of vascular cognitive impairment and neuropathic headache.It is expected to provide a theoretical basis for clinically reasonable and safe use of Tianma Xingnao Capsule.

CLINICAL OBSERVATION ON 67 CASES OF VASCULAR HEADACHE TREATED BY NEEDLING FOR BLOODLETTING PLUS POINT EMBEDDING

Objective: To observe the therapeutic effect of bloodletting plus point implantation of catgut in the treatment of 67 cases of vascular headache. Methods: A total of 107 cases of vascular headache patients were divided into treatment group (n=67) and control group (n=40). Bilateral Taiyang (EX-HN 5) and Jiaosun (TE 20) were pricked with a needle to let a little blood out, once every 4 days. Bilateral Fengmen (BL 12) and Ganshu (BL 18) were used for embedding catgut, once every 16 days. Patients of control group were ordered to take Rotunding, Oryzanol and Nimodipine, 3 times daily. Results: After 16 days’ treatment, of the 67 cases in treatment group, 26 were cured, 37 responded with improvement in their symptoms and 4 failed; while of the 40 cases in control group, 10 were cured, 19 responded with improvement in their symptoms and 11 failed. The total effective rate of treatment group was significantly superior to that of control group (P<0.01). In addition, the time of headache disappearance of treatment group was strikingly shorter than that of control group; while the duration of sleep of treatment group was strikingly longer than that of control group (P<0.01). Conclusion: The therapeutic effect of acupoint bloodletting plus acupoint embedding of catgut is superior to that of Western medicine in the treatment of vascular headache.

Exploring the mechanism of action of Wuzhuyu Decoction for vascular headache based on network pharmacology and molecular docking

Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.

THE STUDY APPLIED ON BA IN PATIENTS WITH VASCULAR HEADACHE

目的:探讨脑电地形图在血管性头痛病人中的应用价值。方法:脑电地形图在血管性头痛病人中被检查了。结果:脑电地形图改变是明显的。结论:脑电地形图在血管性头痛病人中有重要的应用价值。

THE CONTRAST ANALYSIS BETWEEN BA AND REG IN DIAGNOSIS OF PATIENTS WITH VASCULAR HEADACHE

目的: 探讨脑电地形图与脑血流图在血管性头痛患者诊断中的应用价值。方法: 脑电地形图与脑血流图被检查并对患者阳性率进行了对比。结果: 脑电地形图的阳性率是 100%,脑血流图的阳性率是 43. 1%。两者对比 p 值 <0. 05。结论: 脑电地形图在血管性头痛的诊断中有重要价值。

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

TREATMENT OF HISTAMINE HEADACHE WITH ACUPUNCTURE ON DAZHUI(DU 14)

Histamine headache is refractory totreatment.The author treated 2 cases withsuccess and reported in the following is oneof the cases:Mr.Dai ××,a man of 38 years,wasadmitted to the ward on Dec.8,1987.

Clinical Observation on Vascular Headache Treated by Auricular Point Sticking Therapy

Objective： To evaluate the clinical effect of auricular sticking therapy in treating vascular headache. Methods： Fifty patients with vascular headache were randomized into two groups, 25 cases in each. The treatment group received auricular sticking therapy with magnetic pearls, and the control group was treated by Flunarizine Hydrochloride, 30 d as a treatment session, and the results were measured after one treatment session. Result： The total effective rate was 92.0% in the treatment group while 60.0% in the control group, and the difference was significant （P〈0.01）. A marked decrease of blood pressure was detected in the treatment group （P〈0.05）. The mean velocity in middle cerebral artery and anterior cerebral artery both changed significantly （P〈0.01）. Conclusion： Auricular sticking therapy can significantly improve the condition of vascular headache, as well as reduce blood pressure and help cerebral blood flow.

Clinical Observation of Vascular Headache Treated by Acupuncture plus Needle-Embedding Method

Purpose： In order to explore the clinical effect in acupuncture treatment of vascular headache. Methods： 93 cases of vascular headache were randomly auocated into acupuncture group （n= 30）, treated by puncturing Fengchi （GB 20）, Ashi point and Sanyinjiao （SP 6） on the sick side, acupuncture plus needle-embedding group （n= 36）, treated by basic acupuncture treatment plus ncedle-embedding method in Taiyang （Ex HN 5） and Xuanzhong （GB 39） on the sick side, and control group （n = 27）, treated with oral administration of 5 mg Sibelium, twice a day, for observation of the changes in the clinical symptoms before and after treatments in the patients of three groups. Results： After treatment, the clinical symptoms in the patients of three groups were relieved or disappeared. The recent therapeutic effect was better in acupuncture plus needle-embedding group than in the control group （P〈 0.05）, and there was no sig nificant difference （P〉 0.05） between the acupuncture plus needle-embedding group and acupuncture group and there was no significant difference （P〉 0.05）between acupuncture group and control group, either. The long-term therapeutic effect was better in the acupuncture plus ncedle-embedding group than in the control group （P〈 0.01）, in the acupuncture group than in the control group （P 〈 0.05）, and there was no significant difference between the acupuncture plus needle-embedding group and acupuncture group. Conclusion： Acupuncture treatment of vascular headache offers a better recent and longterm therapeutic effect, and acupuncture plus needle-embedding method is much better in the therapeutic effect.

Thirty-two Cases of Vascular Headache Treated by Acupuncture Combined with Chinese Herbal Decoction

To compare the acupuncture plus oral administration of Chinese herbal decoction with simple oral administration of Chinese herbal decoction in the treatment of vascular headache. Methods： Sixty two patients were randomly divided into a treatment group （32 cases） and a control group （30 cases）. Acupuncture at Baihui （GV 20）, Fengchi （GB 20）, Shuaigu （GB 8）, Xingjian （LR 2）, Neiguan （PC 6）, Sanyinjiao （SP 6） and Ashi points combined with oral administration of Chinese herbal decoction, was applied in the treatment group, and simple oral administration of Chinese herbal decoction was applied in the control group. Results： The total therapeutic effect in the treatment group was better than that in the control group （P〈0.05）. After treatment, the frequency, and duration of the attacks were reduced and shortened, and headache greatly alleviated in both groups （P〈0.01）. The alleviation in the treatment group was more obvious than that in the control group （P〈0.05）. Conclusion： Acupuncture combined with oral administration of Chinese herbal decoction provided remarkable therapeutic effects in treating vascular headache.

Review of Vascular Headache Treated by Acupuncture from 1949 to 2004

Summary To review the general situation of acupuncture in treating vascular headache between 1949-2004 in an attempt to promote acupuncture practice, clinical references concerning acupuncture treatment of vascular headache were analyzed on the basis of Chinese Modern Acupuncture Database. From 1956, these references increased annually and steadily. In clini cal practice, needling is cardinally used, and the acupoints are selected adjacent to diseased oart and on syndrome differentiation.

Clinical Observation on the Treatment of 38 Cases of Vascular Headache by Acupuncture

Purpose： This study is to observe the therapeutic effect of puncturing acupoints Dazhui （GV 14）, Fengchi （GB 20）, Jiaji （Ex-B 2）, Waiguan （TE 5）, Qiuxu （GB 40） and Zhaohai （KI 6） on vascular headache. Methods： 68 cases of vascular headache were divided into treatment group including 38 cases and control group including 30 cases. The patients in treatment group were treated by puncturing Dazhui （GV 14）, Fengchi （GB 20）, Jiaji C2-6 （Ex-B 2）, Waiguan （TE 5）, Qiuxu （GB 40） through Zhaohai （KI 6） and patients in control group were asked to take Pizotifen orally. Results： After 2 courses of treatments, 35 cases got effect in treatment group, and 22 cases got effect in control group, the therapeutic effect in treatment group was superior to that in control group （P〈 0.05）. Conclusions： Puncturing Dazhui （GV 14）, Fengchi （GB 20）, Jiaji C2-6（Ex-B 2）, Waiguan （TE 5）, Qiuxu （GB 40） and Zhaohai （KI 6） is effective for the vascular headache.

The role of vascularization in nerve regeneration of nerve graft

Vascularization is an important factor in nerve graft survival and function. The specific molecular regulations and patterns of angiogenesis following peripheral nerve injury are in a broad complex of pathways. This review aims to summarize current knowledge on the role of vascularization in nerve regeneration, including the key regulation molecules, and mechanisms and patterns of revascularization after nerve injury. Angiogenesis, the maturation of pre-existing vessels into new areas, is stimulated through angiogenic factors such as vascular endothelial growth factor and precedes the repair of damaged nerves. Vascular endothelial growth factor administration to nerves has demonstrated to increase revascularization after injury in basic science research. In the clinical setting, vascularized nerve grafts could be used in the reconstruction of large segmental peripheral nerve injuries. Vascularized nerve grafts are postulated to accelerate revascularization and enhance nerve regeneration by providing an optimal nutritional environment, especially in scarred beds, and decrease fibroblast infiltration. This could improve functional recovery after nerve grafting, however, conclusive evidence of the superiority of vascularized nerve grafts is lacking in human studies. A well-designed randomized controlled trial comparing vascularized nerve grafts to non-vascularized nerve grafts involving patients with similar injuries, nerve graft repair and follow-up times is necessary to demonstrate the efficacy of vascularized nerve grafts. Due to technical challenges, composite transfer of a nerve graft along with its adipose tissue has been proposed to provide a healthy tissue bed. Basic science research has shown that a vascularized fascial flap containing adipose tissue and a vascular bundle improves revascularization through excreted angiogenic factors, provided by the stem cells in the adipose tissue as well as by the blood supply and environmental support. While it was previously believed that revascularization occurred from both nerve ends, recent studies propose that revascularization occurs primarily from the proximal nerve coaptation. Fascial flaps or vascularized nerve grafts have limited applicability and future directions could lead towards off-the-shelf alternatives to autografting, such as biodegradable nerve scaffolds which include capillary-like networks to enable vascularization and avoid graft necrosis and ischemia.

Adenomyosis uterine innervation in mice correlates to nerve growth factor expression,inflammation,and vascularization

BACKGROUND： Studies have shown that abnormal innervation is an important factor impacting occurrence and development of pathological pain in endometriosis. OBJECTIVE： To observe uterine innervation of adenomyosis mice and to analyze the cause of innervation changes due to nerve growth factor （NGF） expression, inflammation, and vascularization. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed at the Research Institute of Obstetrics and Gynecology Hospital, and Central Laboratory of Zhongshan Hospital, Fudan University from March to December 2008. MATERIALS： Tamoxifen was provided by Fudan Forward, China. Rabbit anti-mouse NGF was purchased from Santa Cruz Corporation, USA; rabbit anti-protein gene product 9.5 （PGP9.5） and rabbit anti-substance P （SP） were purchased from Chemicon, USA. METHODS： A total of 40 newborn ICR mice were randomly assigned to adenomyosis model and control groups, with 20 animals in each group. Mice in the adenomyosis model group were orally administrated 2.7 μmol/kg tamoxifen on days 2-5 after birth, while the controls were not treated. MAIN OUTCOME MEASURES： Both uteri from all mice were harvested at days 135-145 after birth Expressions of polyclonal PGP9.5 and SP were immunohistochemically detected to demonstrate pan- and sensory nerve fibers. Microvessel density was quantified in the endometrium and myometrium using immunochemical staining for polyclonal rabbit anti-CD31, which stained vessels. Gene expression for NGF, high-affinity tyrosine kinase receptor （trkA）, p75 neuretrophin receptor （p75NTR）, bradykinin receptor-1 （BKR-1）, and 2 （BKR-2）, as well as substance P receptor （neurokininl receptor, NK1-R）, were detected by reverse transcription-polymerase chain reaction. NGF-13 protein expression was detected by Western blot analysis. RESULTS： More nerve fibers were stained with PGP9.5 in the endometrium and myometrium, and with SP in the endometrium, in adenomyosis mice compared with controls （P 〈 0.01 and P 〈 0.05）. Microvessel density in the myometrium of adenomyosis mice was significantly greater than the controls （P 〈 0.01）. In the uterus of adenomyosis mice, mRNA expression of NGF and its two receptors （trkA and p75 NTR）, BKR-1, and NK1-R, as well as protein expression of NGF-β, were greater than the control mice （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Uterine innervation in the adenomyosis mice was increased compared with the controls. Moreover, NGF expression, inflammation, and vascularization, which have been shown to be impact factors of innervation, were abnormal in the uteri of adenomyosis mice.

Nerve Growth Factor and Vascular Endothelial Growth Factor: Retrospective Analysis of 63 Patients with Salivary Adenoid Cystic Carcinoma

Aim To detect the expression of nerve growth factor （NGF） and vascular endothelial growth factor （VEGF） in salivary adenoid cystic carcinoma （SACC） tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. Methodology Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox＇s proportional hazard regression model were applied to assess predictors of survival. Results NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues （P〈0.05）, and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high- expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates （P〈0.05）. Conclusion NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent prognosis factors for survival.

The interaction of stem cells and vascularity in peripheral nerve regeneration

The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration;however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.

Sustained delivery of vascular endothelial growth factor mediated by bioactive methacrylic anhydride hydrogel accelerates peripheral nerve regeneration after crush injury

Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.

Animal models of vascularized nerve grafts:a systematic review

The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts. A systematic literature review on vascularized nerve graft models was conducted via the retrieval with the Pub Med database on March 30, 2019. Data on the animal, nerve, and vascularization model, the recipient bed, the evaluation time points and methods, and the results of the study results were extracted and analyzed from selected articles. The rat sciatic nerve was the most popular model for vascularized nerve grafts, followed by the rabbit;however, rabbit models allow for longer nerve grafts, which are suitable for translational evaluation, and produced more cautious results on the superiority of vascularized nerve grafts. Compared to free nerve grafts, vascularized nerve grafts have better early but similar long-term results, especially in an avascular bed. There are few studies on avascular receiving beds and prefabricated nerve grafts. The clinical translation potential of available animal models is limited, and current experimental knowledge cannot fully support that the differences between vascularized nerve grafts and free nerve grafts yield a clinical advantage that justifies the complexity of the procedure.