1.Modified Tongqiao Huoxuetang Down-regulates PI3K/Akt Pathway to Treat Basilar Artery Dolichoectasia
Feixiang LIU ; Daopei ZHANG ; Zhaoxin WU ; Huailiang ZHANG ; Yunke ZHANG ; Jinxin MIAO ; Zhenqiang ZHANG ; Ruiqin SUN ; Lixiang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):87-94
ObjectiveTo establish a mouse model of basilar artery dolichoectasia (BAD) and explore the mechanism of modified Tongqiao Huoxuetang (JTQHX) in regulating BAD via phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. MethodSixty C57/BL6 female mice were randomized into sham operation (injected with 10 U·mL-1 inactivate elastase), model, atorvastatin calcium tablets (2.6 mg·kg·d-1), and low- and high-dose (crude drug 3.4, 17 g·kg-1·d-1, respectively) JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL-1 elastase. After 14 days of modeling, the sham operation group and model group were administrated with equal volumes of pure water by gavage, and other groups with corresponding drugs for 2 months. The levels of interleukin-6 (IL-6) and calpain (LpA) in the serum were measured by enzyme-linked immunosorbent assay (ELISA). Verhoeff 's Van Gieson (EVG) staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was employed to examine the apoptosis rate of vascular smooth muscle cells (VSMCs). Image Pro Plus was used to observe and calculate the curvature index, elongation length, percentage increase in vessel diameter, and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group, the model group showed lowered IL-6 level (P<0.01), no significant change in LpA level, increased apoptosis of VSMCs (P<0.01), and increased curvature index, elongation length, percentage increase in vessel diameter, and curvature angle (P<0.01). Furthermore, the modeling up-regulated the protein levels of PI3K and Akt in blood vessels (P<0.01) and aggravated the destruction of the inner elastic layer, atrophy of the muscular layer, and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group, 2 months of treatment with JTQHX elevated the IL-6 level (P<0.01), reduced the apoptosis of VSMCs (P<0.01), decreased the curvature index, elongation length, percentage increase in vessel diameter, and curvature angle (P<0.05, P<0.01), and down-regulated the protein levels of PI3K and Akt in blood vessels (P<0.01). In addition, the treatment alleviated the destruction of the inner elastic layer, atrophy of the muscular layer, and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation, expansion, and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.
2.Research Progress on the Pathogenesis of Vestibular Migraine-related Visual Vertigo
Yuge NIU ; Daopei ZHANG ; Huailiang ZHANG
Journal of Audiology and Speech Pathology 2024;32(1):85-89
Vestibular migraine(VM)is a common vestibular disorder in which vertigo and migraine coexist,and visually induced vertigo is one of the typical vestibular symptoms of VM.The clinical manifestations of VM re-lated visual vertigo are various,which are affected by anxiety,motion sickness,age and other factors.Multiple mechanisms such as anatomical and physiological connections,gaze instability,visual vestibular integration defects,impaired sensory remodeling,sensitization of the central vestibular pathway,5-hydroxytryptamine and glutamate-glutamine cycle and other neurotransmitters may lead to VM-related visual vertigo.
3.Recent advance in migraine with brainstem aura associated with transient loss of consciousness
Mingkai HOU ; Daopei ZHANG ; Huailiang ZHANG
Chinese Journal of Neuromedicine 2024;23(9):947-953
Migraine with brainstem aura is one of the subtype of migraine with aura, with varied etiology and complex mechanism. Migraine with brainstem aura and transient loss of consciousness (TLOC) often occur together clinically, seriously affect the social life of the patients. At present, relation between migraine with brainstem aura and TLOC has not been elucidated, and clinical manifestations between TLOC and syncope is similar and easily confused by physicians. In order to deeply explore the complex relations between migraine with brainstem aura and TLOC, this article summarizes the clinical association, pathogenesis and differential diagnosis of migraine with brainstem aura associated with TLOC, so as to further optimize the clinical diagnosis strategies and provide new ideas for exploring comprehensive treatment measures for migraine with brainstem aura associated with TLOC.
4.Exploration of pathogenesis and treatment of epilepsy based on astrocyte energy metabolism
Zihao ZHANG ; Yiming LI ; Weitao WANG ; Daopei ZHANG ; Huailiang ZHANG
Chinese Journal of Neuromedicine 2024;23(10):1069-1073
Astrocytes play a key role in maintaining the homeostasis and function of the central nervous system. Abnormal lipid accumulation, ferroptosis, elevated lactic acid, and high DNA methylation mediated by astrocytes in their own or toxic states are particularly closely related to seizures. In recent years, epilepsy treatment from astrocyte energy metabolism perspective has become a research hotspot. Metabolic therapy, such as ketogenic diet, can inhibit seizures via a variety of mechanisms as astrocyte homeostasis maintenance. This paper reviews the relationship between astrocyte energy metabolism and epilepsy pathogenesis and its related metabolic therapy, in order to provide new ideas for clinical treatment of drug-resistant epilepsy.
5.Animal models of vertebrobasilar dolichoectasia
Xi LI ; Huailiang ZHANG ; Daopei ZHANG
International Journal of Cerebrovascular Diseases 2023;31(6):472-476
Vertebrobasilar dolichoectasia (VBD) is a cerebrovascular variant disease. Researches have shown that further development of VBD may lead to severe disability and even death. The pathogenesis of VBD is still unclear, and there is no specific clinical prevention and treatment scheme. Therefore, establishing a stable and reliable animal model helps to further understand the pathophysiological mechanisms and potential therapeutic targets of VBD. This article reviews the establishment methods and research progress of the available VBD animal models.
6.Relationship between diet and migraine: induction and treatment
Zihao ZHANG ; Yiming LI ; Daopei ZHANG ; Huailiang ZHANG
Chinese Journal of Neuromedicine 2023;22(11):1169-1174
Diet can be both a trigger and a treatment for migraine. The effects of alcohol, dairy products and pickled foods on migraine have been highly recognized. The effects of plant foods and caffeine on migraine currently have 2 sides. Ketogenic diet (KD), modified Atkins diet (MAD), and high n-3 fatty acid/low n-6 fatty acid diet can improve migraine through protecting nerves, improving mitochondrial function and energy metabolism, reducing calcitonin gene-related peptide (CGRP) levels, and inhibiting neuroinflammation. In this paper, the recent advance in the above content is summarized as follows.
7.Research progress on the correlation between visual factors and persistent postural- perceptual dizziness symptoms
Yinmeng YANG ; Daopei ZHANG ; Huailiang ZHANG
Chinese Journal of Neurology 2022;55(11):1330-1334
Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disease. Related studies have shown that PPPD patients often show high visual dependence in posture control or spatial orientation activities, and the symptoms are aggravated in visual motor stimulation or complex visual environment. The visual dependence of PPPD patients may be related to age factors, anxiety symptoms, visual-vestibular system interaction and neurotransmitter changes. A correct understanding of the relationship between vision and PPPD can provide more help for the clinical diagnosis and treatment of PPPD in the future. This article reviews the correlation and possible mechanism between visual factors and clinical symptoms of PPPD.
8.Elastase injection into the cerebellomedullary cistern to induce a model of vertebrobasilar dolichoectasia in mice and evaluation of magnetic resonance angiography
Weitao WANG ; Lixia YANG ; Daopei ZHANG ; Suo YIN ; Feixiang LIU ; Huailiang ZHANG
International Journal of Cerebrovascular Diseases 2021;29(9):685-688
Objective:To investigate the effect of magnetic resonance angiography (MRA) in evaluating the mouse model of vertebrobasilar dolichoectasia (VBD) induced by injection of elastase into cerebellomedullary cistern.Methods:Twenty-four male C57/BL6 mice were selected. The mice in the elastase group ( n=12) were injected in the cerebellomedullary cistern with 2.5 μl of phosphate buffer containing 25 mU elastase, and the mice in the saline control group ( n=12) were injected with the same volume of normal saline. MRA examination of the brains of living mice was performed 2 weeks after modeling. Successful modeling was defined as the basilar artery bending angle ≤170°, or the basilar artery bending length accounts for ≥10%, or the basilar artery deviated from the midline by more than 1 grade, or the percentage increase in artery diameter was ≥25%. Results:In the elastase group and the saline control group, 2 mice and 1 mouse did not wake up normally or died, respectively. The 11 surviving mice in the saline control group had no obvious vertebral artery and basilar artery abnormalities. The success rate of modeling in the 10 surviving mice in the elastase group was 80%, and the difference in the success rate between the two groups was statistically significant ( P<0.05). There were significant differences in mean basilar artery diameter (0.30 mm vs. 0.22 mm; P<0.05), mean basilar artery bending angle (115° vs. 170°; P<0.05), and proportion of mean basilar artery bending length (31% vs. 5%; P<0.05) of the surviving mice between the elastase group and the saline control group. Conclusion:MRA can better evaluate the mouse VBD model induced by elastase injection in the cerebellomedullary cistern.
9.Early diffusion-weighted imaging-negative posterior circulation stroke presenting as isolated vascular vertigo
Daopei ZHANG ; Weitao WANG ; Feixiang LIU ; Huailiang ZHANG ; Mingjun ZHU
International Journal of Cerebrovascular Diseases 2020;28(3):206-211
Posterior circulation ischemic stroke can be manifested as isolated vertigo, and the posterior circulation small infarcts often show early negative diffusion-weighted imaging, which is likely to cause misdiagnosis and missed diagnosis. Summarizing the characteristics and screening strategies of these patients can provide help for timely diagnosis and selection of effective treatment strategies.
10.Analysis of Flavonoids Chemical Components in Waste Material during Industrialization of Pueraria thomsonii Resources
Huiting ZENG ; Chao CHEN ; Huailiang CHU ; Shaoqing ZHU ; Yuanjian YUAN ; Xiaoqing WANG ; Jianhua ZHANG ; Jinbao YU ; Jing LI
China Pharmacy 2020;31(4):451-456
OBJECTIVE:To study the composition and contents of flavonoids chemical components in waste material during industrialization of Pueraria thomsonii resources,and to provide reference for comprehensive development and reasonable utilization of the variety. METHODS :Using“No. 2 Gange”of P. thomsonii from Jiangxi as objects ,UPLC-Q-TOF-MS and HPLC method were adopted to detect the components and contents of flavonoids in the root (with or without cortex ),cortex,flower, fibrous root ,stem,head and dregs (with or without cortex )of P. thomsonii as well as dry matter of industrial wastewater (with or without cortex )after precipitation of pueraria powder. RESULTS :The linearity ,precision,repeatability,stability and recovery of the established method for content determination of 7 flavonoids(puerarin,daidzin,iridoxine-7-O-xylose glucoside ,genistin, iridin,daidzein and kakkalide )were all in line with the requirements. Totally 12 kinds of flavonoids were identified ,among which the flavonoids in the root ,cortex,stem,fibrous root ,head and dregs of P. thomsonii as well as dry matter of industrial wastewater were the same ,mainly were puerarin ,daidzin,genistein,daidzein and malonyl-daidzein. The flower of P. thomsonii mainly included iridoxine- 7-O-xylose glucoside ,genistin,iridin,kakkalide,6″-O-xylosyldaidzein,but the components as puerarin , daidzin and its aglycone were not be detected. The content of puerarin in the head of P. thomsonii was the highest (5.765%). The contents of puerarin in root and dregs of P. thomsonii as well as dry matter of industrial waste-water in samples with cortex were all higher than in corresponding peeled sample. CONCLUSIONS :The waste material from the industrialization of P. thomsonii resources contains a lot of flavonoids with rich species and high content ,and can be used as an important raw material for obtaining flavonoids such as puerarin.

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