Correlation of vascular endothelial growth factor to permeability of blood-brain barrier and brain edema during high-altitude exposure

BACKGROUND： Many studies have evaluated the role of vascular endothelial growth factor （VEGF） in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE： To observe the effects of VEGF expression on permeability of the blood-brain barrier （BBB） during high-altitude and hypoxia exposure, and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure. DESIGN, TIME AND SETTING： The randomized, controlled, animal study was performed at the Tanggula Etape, Central Laboratory of Chengdu Medical College, and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA, China, from July 2003 to November 2004. MATERIALS： Quantitative RT-PCR kit （Sigma, USA）, VEGF ELISA kit （Biosource, USA）, and Evans blue （Jingchun, China） were acquired for this study. METHODS： A total of 180 Wistar rats were equally and randomly assigned to 15 groups： low-altitude （500 m）, middle-altitude （2 880 m）, high-altitude （4 200 m）, super-high-altitude （5 000 m）, 1,3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days of super high-altitude exposure. Wistar rats were exposed to various altitude gradients to establish a hypoxia model. MAIN OUTCOME MEASURES： Brain water content was calculated according to the wet-to-dry weight ratio. BBB permeability to Evans blue was determined by colorimetric method. VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA. RESULTS： Brain water content, BBB permeability to Evans blue, and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude. The greatest increase was determined on day 9 upon ascending 5 000 m. Simultaneously, VEGF expression positively correlated to BBB permeability of Evans blue and brain water content （r = 0.975, 0.917, P〈 0.01）. CONCLUSION： Increased VEGF protein and mRNA expression was responsible for increased BBB permeability, which may be an important mechanism underlying brain edema during high-altitude exposure.

Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

Regulatory effect of vascular endothelial growth factor on blood spinal cord barrier in presyrinx state of experimental syringomyelia

BACKGROUND： Vascular endothelial growth factor （VEGF） is able to regulate blood spinal cord barrier function as well as influence neovascularization and cause edema. OBJECTIVE： Through establishment of a rabbit model of syringomyelia, to explore the correlation between VEGF protein and mRNA expressions and function of blood spinal cord barrier and edema degree of spinal cord in presyrinx state. DESIGN, TIME AND SETTING： Randomized controlled animal study was performed in the Tumor Institute of the Fourth Hospital, Hebei Medical University from January to June 2007. MATERIALS： Atotal of 0.6 mL Kaolin solution （250 g/L, 37℃） was injected into the cisterna magna of 40 rabbits in the kaolin group to establish syringomyelia models. Goat anti-rabbit VEGF monoclonal antibody was provided by DIACLONE Company, USA; RT-PCR related reagents were provided by Huamei Bioengineering Co., Ltd., Beijing. METHODS： Sixty Chinese white rabbits were divided randomly into two groups： Kaolin group （n = 40） and control group （n = 20）. Physiological saline （0.6 mL at 37℃） was injected in rabbits of control group. On days 1,3, 7, 14 and 21 after kaolin injection, cervical cords samples were harvested after sacrifice of animal. MAIN OUTCOME MEASURES： VEGF protein and mRNA expressions were detected by immunohistochemistry and RT-PCR on days 1, 3, 7, 14, and 21 after kaolin injection. A quantitative analysis of blood spinal cord barrier function was performed by Evans blue technique. Water content of the spinal cord was measured by dry-wet weight technique. The correlation between the expression of VEGF protein and mRNA and the function of blood spinal cord barrier in the upper cervical cord of the presyrinx state was analyzed by linear correlation analysis. RESULTS： The water content and Evans blue content increased in the kaolin group on days 1 and 3 postoperatively compared with the control group （F = 7.387, 61.35, P 〈 0.05, 0.01）, and reached a peak on day 7 （F = 135.94, 528.35, P 〈 0.01）. They declined slowly to day 21 postoperatively, but both contents were still higher than the control group （F = 11.51, 58.63, P 〈 0.01）. VEGF protein expression increased on day 1, and stronger positive expression was seen on days 3, 7 and 14. It decreased on day 21. VEGF protein expression was higher than the control group at each time point （F = 137.4-468.5, P 〈 0.01 ）. VEGF mRNA expression showed the same pattern in the cervical cord at different time points. By statistical analysis, the expression of VEGF protein and mRNA had a significantly positive correlation with the structural and functional changes of the blood spinal cord barrier in the presyrinx state （r = 0.604-0.979, P 〈 0.05）. CONCLUSION： In the presyrinx state of syringomyelia, the expressions of VEGF protein and mRNA can influence the structure and function of the blood spinal cord barrier and play an important role in the formation and development of spinal cord edema and syringomyelia.

Changes in blood-brain barrier permeability and expression of related factors in a rat model of intracerebral hemorrhage following minocycline treatment

Inflammatory factor aggregation and blood-brain barrier（BBB）damage occur around hematoma foci following intracerebral hemorrhage.Minocycline is lipophilic,can pass through the BBB,and shows anti-inflammatory effects in models of central nervous system disease.We found that minocycline application at 6 hours after intracerebral hemorrhage reduced BBB permeability,decreased vascular endothelial growth factor expression,and increased nerve growth factor and heat shock protein 70 expression,primarily in neurons and microglia.Early intraperitoneal injection of minocycline attenuated BBB damage possibly by reducing vascular endothelial growth factor expression and enhancing nerve growth factor and heat shock protein 70 expression.

Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.

Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca2+ and cyclic adenosine monophosphate levels through PI3K/AKT pathway

BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.

Functions of Müller cell-derived vascular endothelial growth factor in diabetic retinopathy

Müller cells are macroglia and play many essential roles as supporting cells in the retina.To respond to pathological changes in diabetic retinopathy(DR),a major complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascular endothelial growth factor(VEGF or VEGF-A).As VEGF is expressed by multiple retinal cell-types and Müller glia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function of VEGF or other globally expressed proteins produced by Müller cells.With the development of conditional gene targeting tools,it is now possible to dissect the function of Müller cell-derived VEGF in vivo.By using conditional gene targeting approach,we demonstrate that Müller glia are a major source of retinal VEGF in diabetic mice and Müller cell-derived VEGF plays a significant role in the alteration of protein expression and peroxynitration,which leads to retinal inflammation,neovascularization,vascular leakage,and vascular lesion,key pathological changes in DR.Therefore,Müller glia are a potential cellular target for the treatment of DR,a leading cause of blindness.

Transforming growth factor-β and peripheral regulatory cells are negatively correlated with the overall survival of hepatocellular carcinoma

AIM To understand the cellular and molecular changes inperipheral blood that can lead to the development of hepatocellular carcinoma(HCC) and provide new methods for its diagnosis and treatment.METHODS Peripheral blood mononuclear cells were isolated from the peripheral blood of HCC patients and normal controls and then analyzed by flow cytometry. The percentage of transforming growth factor-β(TGF-β)+ regulatory cells(Tregs) in the peripheral blood was measured, and the expression of TGF-β was also determined. Then, the relationship between the changes and the 5-year survival of patients was analyzed. In addition, recombinant human TGF-β(rh TGF-β) and recombinant human interleukin-6 were added to stimulate the cultured cells, and their effects on HCC were evaluated.RESULTS The expression of TGF-β and the percentage of TGF-β+ Tregs in the peripheral blood of HCC patients increased significantly compared with normal controls. Compared with the low TGF-β expression group, the high TGF-β expression group had a significantly lower 5-year survival rate, and the same result was found in the two TGF-β+ Treg groups, suggesting that TGF-β and TGF-β+ Tregs were negatively correlated with the overall survival of the patients. In addition, rh TGF-β promoted the growth of tumor cells and induced high expression levels of IL-6, which further promoted tumor proliferation.CONCLUSION The results showed that TGF-β may promote tumor growth and proliferation by inducing the production of IL-6, and TGF-β and TGF-β+ Tregs may serve as new markers for predicting a poor prognosis in HCC.

Vascular endothelial growth factor A promotes platelet adhesion to collagen Ⅳ and causes early brain injury after subarachnoid hemorrhage

The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.

Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.

Regulation Effect of Vascular Endothelial Growth Factor on Human Fetal Choroid Vascularization

Purpose:To investigate the spatial and temporal regulation effect of vascular endothelial growth factor(VEGF)on human fetal choroid vascularization.Methods:The eyeballs of 54human fetuses from the 9th week to the40th week due to accidental abortion were studied by immunohistochemically staining for the expression of VEGF and proliferation cell nuclear antigen(PCNA).Results:(1)The distribution of VEGF expression in the retinal pigment epithelium(RPE)decreased with the increase of age,the peak of which was between the 9th and 14th week,(2)PCNAimmunoreactivity was localized within choriocapillaris endothe-lium,THe expression level decreased alone with fetus age,In this period the chori-ocapillaris endothelium kept proliferation,differentiation.canalization and remodelled to form the choroid vessels.(3)Statistically significant correlations were shown between the expression of VEGF in the PRE and that of PCNAin choriocapillaris endothelium(r=0.933,P<0.01).Conclusion:VEGF expression in PRE was positively involved in modulating human fetal choroid vascularization.Eye Science2000;16:11-14.

Initial research of cord blood leptin, adiponectin and IGF-I with fetus growth and development

Objective:In order to reveal the relationship between cord blood leptin,adiponectin and insulin-like growth factor-I(IGF-I)and the fetus growth and development,and discuss the interaction and clinical significance on fetus growth and development.Methods:The levels of cord blood leptin,adiponectin,IGF-I in 86 newborns were examined by radio immunoassay,according to gestation age and birth weight percentile relation,the objects were divided into the SGA group(n=16),the AGA group(n=41),the LGA group(n=29),meanwhile,neonatal birth weight,body length,head circumference,foot length,and placental weight were measured,and body mass index(BMI)was computed.Dependability analysis was taken.Results:The levels of cord blood leptin,adiponectin and IGF-I were as follows:LGA group>AGA group>SGA group.The level of cord blood adiponectin was positively correlated with birth weight,placental weight and BMI(p<.05).Cord blood leptin and IGF-I concentrations were positively correlated with their birth weight,body length,head circumference,foot length,placental weight and BMI,respectively(p<.01),cord blood leptin was positively correlated with adiponectin and IGF-I(p<.01).The levels of cord blood leptin and adiponectin had no statistical significance with neonatal sexuality and deliver style(p>.05);the levels of cord blood IGF-I had no statistical significance with neonatal sexuality(p>.05),but had statistical significance with deliver style(p<.05).Conclusions:Cord blood leptin,adiponectin and IGF-I played an important part in adjusting fetus growth and development as well as participating in the process of fetus growth and development,and could be regarded as one of the clinical indexes to evaluate fetus growth and development or state of nutrition.The abnormal level of cord blood leptin and IGF-I might be one of the reasons to cause intrauterine growth retardation and fetal macrosomia.

Regulation effect of vascular endothelial growth factor on vascularization and angiogenesis in developmental human fetal retinas

目的 :研究血管内皮生长因子 ( Vascular endothelial growth factor VEGF)对人胚胎视网膜血管发生的调节作用。方法 :收集 54例 9～ 4 0周龄胎儿眼球后壁标本 ,免疫组织化学染色 ,光镜观察。结果 :1VEGF在视网膜的表达呈波峰式分布 ,高峰在 9～ 13周及 2 6周左右。 2节细胞层的梭形细胞(血管内皮细胞前体细胞 )、血管内皮细胞呈增殖细胞核抗原 ( Proliferation cell nucelear antigen,PCNA)免疫反应阳性 ,水平波动 ,高峰在 9～ 13周及 2 1周前后 ,此期间梭形细胞不断增殖、分化形成内皮细胞索 ,经改建形成视网膜内层血管 ,2 6、34周起见内核层内、外缘血管内皮细胞呈 PCNA免疫反应阳性 ,并保持至足月。 3视网膜 VEGF表达量与梭形细胞、血管内皮细胞 PCNA表达量呈显著正相关( r=0 .736,P<0 .0 1)。结论

低负荷血流限制和高强度抗阻运动对男性运动青年大腿微循环功能的影响

背景:微循环作为人体物质能量代谢交换的唯一场所,与人体运动能力密切相关。抗阻运动是提高微循环功能的有效方式,但也有研究指出血流限制训练也能提高微循环功能,且具有负荷小和安全性高等优点。目的:比较6周低负荷血流限制运动、高强度抗阻运动对运动型男性青年大腿微循环功能的影响,并从血管内皮功能角度探讨运动改善微循环功能的可能机制。方法:将湖北民族大学60名体育专业男性大学生按照随机数表法分为对照组、高强度抗阻运动组和低负荷血流限制运动组,每组20人。低负荷血流限制运动组进行6周(每周3次、每次90 min、运动强度为30%1RM)的低负荷血流限制运动;高强度抗阻运动组进行6周(每周3次、每次90 min、运动强度为70%1RM强度)的抗阻训练;对照组该时间段不进行任何形式的运动训练。分别在干预开始的前1 d以及6周干预结束后次日的晨起空腹状态下对3组受试者微血管血流灌注量、经皮氧分压、肌氧饱和度、一氧化氮、内皮型一氧化氮合酶、内皮素1、血管内皮细胞生长因子及大腿围、肌力等指标进行测试。结果与结论:①运动干预后,低负荷血流限制运动组和高强度抗阻运动组的微血管血流灌注量加热值、血细胞移动速度加热值与对照组及运动干预前相比有显著差异(P<0.05);低负荷血流限制运动组微血管血流灌注量加热值、血细胞移动速度加热值与高强度抗阻运动组相比有显著差异(P<0.05);经皮氧分压和肌氧饱和度与干预前相比有显著性差异(P<0.05)。②运动干预后,低负荷血流限制运动组和高强度抗阻运动组一氧化氮、内皮型一氧化氮合酶、内皮素1、血管内皮细胞生长因子与对照组及运动干预前相比有显著差异(P<0.05)。③运动干预后,低负荷血流限制运动组和高强度抗阻运动组大腿围和大腿肌肉力量与运动干预前相比有显著差异(P<0.05)。④上述结果证实,6周低负荷血流限制运动和高强度抗阻运动可能通过调节内皮型一氧化氮合酶、内皮素1、血管内皮细胞生长因子等血管因子的分泌,提高体育专业大学生大腿微循环功能,并增加大腿肌肉的收缩力量,且低负荷血流限制运动对微血管血流灌注量、血细胞移动速度的干预效果更佳,因此低负荷血流限制运动较高强度抗阻运动在提高微循环功能方面更具优势。

Transplantation of human umbilical cord blood mesenchymal stem cells to treat a rat model of traumatic brain injury

In the present study, human umbilical cord blood mesenchymal stem cells were injected into a rat model of traumatic brain injury via the tail vein. Results showed that 5-bromodeoxyuridine-labeled cells aggregated around the injury site, surviving up to 4 weeks post-transplantation. In addition, transplantation-related death did not occur, and neurological functions significantly improved. Histological detection revealed attenuated pathological injury in rat brain tissues following human umbilical cord blood mesenchymal stem cell transplantation. In addition, the number of apoptotic cells decreased. Immunohistochemistry and in situ hybridization showed increased expression of brain-derived neurotrophic factor, nerve growth factor, basic fibroblast growth factor, and vascular endothelial growth factor, along with increased microvessel density in surrounding areas of brain injury. Results demonstrated migration of transplanted human umbilical cord blood mesenchymal stem cells into the lesioned boundary zone of rats, as well as increased angiogenesis and expression of related neurotrophic factors in the lesioned boundary zone.

Functional recovery and microenvironmental alterations in a rat model of spinal cord injury following human umbilical cord blood-derived mesenchymal stem cells transplantation

BACKGROUND： Transplantation of human umbilical cord blood-derived mesenchymal stem cells （MSCs） has been shown to benefit spinal cord injury （SCI） repair. However, mechanisms of microenvironmental regulation during differentiation of transplanted MSCs remain poorly understood. OBJECTIVE： To observe changes in nerve growth factor （NGF）, brain-derived neurotrophic factor （BDNF）, and interleukin-8 （IL-8） expression following transplantation of human umbilical cord-derived MSCs, and to explore the association between microenvironment and neural functional recovery following MSCs transplantation. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Soochow University from April 2005 to March 2007. MATERIALS： Human cord blood samples were provided by the Department of Gynecology and Obstetrics, First Affiliated Hospital of Soochow University. Written informed consent was obtained. METHODS： A total of 62 Wister rats were randomly assigned to control （n = 18）, model （n = 22, SCI ＋ PBS）, and transplantation （n = 22, SCI ＋ MSCs） groups. The rat SCI model was established using the weight compression method. MSCs were isolated from human umbilical cord blood and cultured in vitro for several passages. 5-bromodeoxyuridine （BrdU）-Iabeled MSCs （24 hours before injection） were intravascularly transplanted. MAIN OUTCOME MEASURES： The rats were evaluated using the Basso, Beattie and Bresnahan （BBB） locomotor score and inclined plane tests. Transplanted cells were analyzed following immunohistochemistry. Enzyme-linked immunosorbant assay was performed to determine NGF, BDNF, and IL-8 levels prior to and after cell transplantation. RESULTS： A large number of BrdU-positive MSCs were observed in the SCI region of the transplantation group, and MSCs were evenly distributed in injured spinal cord tissue 1 week after transplantation. BBB score and inclined plane test results revealed significant functional improvement in the transplantation group compared to the model group （P 〈 0.05）, which was maintained for 2-3 weeks. Compared to the model group, NGF and BDNF levels were significantly increased in the injured region following MSCs transplantation at 3 weeks （P 〈 0.05）, but IL-8 levels remained unchanged （P 〉 0.05）. CONCLUSION： MSCs transplantation increased NGF and BDNF expression in injured spinal cord tissue. MSCs could promote neurological function recovery in SCI rats by upregulating NGF expression and improving regional microenvironments.

Effects of Chinese Herbal Compound on the Blood Physiological Indices and Cytokines of Myelosuppressive Mice

[ Objective ] The research aimed to study the effects of Chinese herbal compound on the blcod physiological indices and cytokines of myelosuppressive mice. [ Metho] Myelasuppressive mice model was established by intraperitoneal injection of 80 mg/kg cyclophosphamide. Chinese herbal compound was composed of Houttuynia cordata, Taraxacum mongolicum, Citrus reticulata peel, Atractylodes chinensis, Paeonia sterniana, Atractylodes macrocephala and Angelica sinensis. The effects of Chinese herbal compound and Astragalus polysaccharide at different doses on the blood physiological indices and hematopoietic growth factors of myelosuppressive mice were discussed. [ Result] Myelosuppressive mice medel was successfully established. The total white blood cell count, total nentrephile granulocyte count, total lymphocyte count, total platelet count and the contents of serum interleukin-6 and erythropoietin in myelosuppressive mice were significantly decreased. The total erythrocyte count, the contents of hemoglobin and imerleukin-3 were decreased, without significant difference. The blood physiological indices and the contents of interleukin-3 and erythropoietin in myelosuppressive mice could be improved by intragastric administration of Astragalus polysaccharide and Chinese herbal compound at different doses for 3 days or 7 days. The effect of 20 g/kg Chinese herbal compound was the best after administration for 3 days, and the effect of 10 g/kg Chinese herbal compound was the best after administration for 7 days. The total white blcod cell count, total neutrophile granulocyte count, percentage of neutrephile granulocyte, total lymphocyte count, total count of middle cells, percentage of middle cells, total platelet count, contents of interleukin-3 and erythropoietin in myelosuppressive mice could be extremely significantly improved by intragastric administration of 10 g/kg Chinese herbal compound for 7 days（ P 〈 0. 01 ） , and the reduction of red blood cell count, hematecfit, the contents of hemoglobin and interleukin-6 induced by cyclophesphamide could be inhibited （P 〈 0.01 ）. [ Conclusion ] Chinese herbal compound could improve the hematopoietic function of myclosuppressivc mice induced by cyclophosphamide and its effect was better than Astragalus polysaccharide. 20 g/kg Chinese herbal compound reacted fast and the reaction of 10 g/kg Chinese herbal compound was slow ,but its efficacy was lasting.

Electro-acupuncture at Conception and Governor vessels and transplantation of umbilical cord bloodderived mesenchymal stem cells for treating cerebral ischemia/reperfusion injury

Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper- fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/ reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at 24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry findings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the isch- emic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These findings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promot- ing neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.

Preliminary investigation of tumor angiogenesis and blood flow pattern in solitary bronchogenic adenocarcinoma: radiologic-pathologic correlation

Objective: To investigate the correlations of vascular endothelial growth factor (VEGF)-positive tumor angiogenesis and the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma. Methods: 30 patients with VEGF-positive bronchogenic adenocarcinomas (diameter ≤ 4 cm) underwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 mL/sec by using an autoinjector) serial CT. The quantifiable parameters (Perfusion, peak height, ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta and mean transit time) of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma were compared with microvessel densities (MVDs) and VEGF expression by immunohistochemistry. Results: Peak height of VEGF-positive bronchogenic adenocarcinoma was 36.06 HU ± 13.57 HU, bronchogenic adenocarcinoma-to-aorta ratio 14.25% ± 4.92, and perfusion value 29.66 ± 5.60 mL/min/100 g , mean transit time 14.86 s ± 5.84 s, and MVD 70.15 ± 20.03. Each of peak height, ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta and perfusion correlated positively with MVD (r = 0.781, P < 0.0001; r = 0.688, P < 0.0001; r = 0.716, P < 0.0001; respectively). No significant correlation was found between mean transit time and MVD (r = 0.260, P = 0.200 > 0.05). Conclusion: Perfusion, peak height and ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta reflect MVD in VEGF-positive bronchogenic adenocarcinoma. Perfusion, peak height and ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta derived with dynamic CT might be index for VEGF-related tumor angiogenesis in bronchogenic adenocarcinoma.

Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy

Objective:Oncocardiology is increasingly hot research field/topic in the clinical management of cancer with anti-angiogenic therapy of vascular endothelial growth factor(VEGF)that may cause cardiovascular toxicity,such as hypertension via vascular dysfunction and attenuation of eNOS/NO signaling in the baroreflex afferent pathway.The aim of the current study was to evaluate the potential roles of VEGF/VEGF receptors(VEGFRs)expressed in the baroreflex afferent pathway in autonomic control of blood pressure(BP)regulation.Methods:The distribution and expression of VEGF/VEGFRs were detected in the nodose ganglia(NG)and nucleus of tractus solitary(NTS)using immunostaining and molecular approaches.The direct role of VEGF was tested by NG microinjection under physiological and hypertensive conditions.Results:Immunostaining data showed that either VEGF or VEGFR2/VEGFR3 was clearly detected in the NG and NTS of adult male rats.Microinjection of VEGF directly into the NG reduced the mean blood pressure(MBP)dose-dependently,which was less dramatic in renovascular hypertension(RVH)rats,suggesting the VEGF-mediated depressor response by direct activation of the 1st-order baroreceptor neurons in the NG under both normal and disease conditions.Notably,this reduced depressor response in RVH rats was directly caused by the downregulation of VEGFR2,which compensated the up regulation of VEGF/VEGFR3 in the NG during the development of hypertension.Conclusion:It demonstrated for the first time that the BP-lowering property of VEGF/VEGFRs signaling via the activation of baroreflex afferent function may be a common target/pathway leading to BP dysregulation in anti-angiogenic therapy.