Application of MOTOmed in stepped individualized rehabilitation intervention of older adult patients with post-stroke hemiplegia / 中国基层医药

Objective:To investigate the application effects of MOTOmed in stepped individualized rehabilitation intervention of older adult patients with post-stroke hemiplegia.Methods:A total of 130 older adult patients with post-stroke hemiplegia who received treatment in the Affiliated People's Hospital of Ningbo University from June 2019 to June 2021 were included in this study. They were randomly assigned to undergo either stepped individualized rehabilitation intervention with MOTOmed training system (observation group, n = 65) or routine rehabilitation intervention (control group, n = 65) for 1 month. Before and after intervention, the Fugl- Meyer Assessment score, Berg Balance Scale score, Functional Ambulation Category scale score, modified Ashworth scale score, and modified Barthel Index, Self-Perceived Burden Scale score, nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3 levels were compared between the two groups. Results:After intervention, Fugl-Meyer Assessment and Berg Balance Scale scores in the observation groups were (75.48 ± 6.54) points and (48.55 ± 5.18) points, which were significantly greater than (72.55 ± 6.33) points and (46.50 ± 4.79) points in the control group ( t = 2.59, 2.34, both P < 0.05). Functional Ambulation Category scale score in the observation group was significantly higher than that in the control group [(3.22 ± 0.43) points vs. (3.05 ± 0.39) points, t = 2.36, P < 0.05). Modified Ashworth scale score in the observation group was significantly lower than that in the control group [(1.23 ± 0.24) points vs. (1.33 ± 0.26) points, t = 2.27, P < 0.05). Modified Barthel Index score in the observation group was significantly higher than that in the control group [(59.32 ± 5.18) points vs. (57.33 ± 4.92) points, t = 2.24, P < 0.05]. There was no significant difference in Self-Perceived Burden Scale score between the two groups ( t = 1.64, P > 0.05). Nerve growth factor level in the observation group was significantly higher than that in the control group [(12.93 ± 2.31) ng/L vs. (12.06 ± 2.29) ng/L, t = 2.15, P < 0.05]. There were no significant differences in brain-derived neurotrophic factor and neurotrophin 3 levels between the two groups ( t = 0.91, 1.25, both P > 0.05). Conclusion:The stepped individualized rehabilitation intervention with MOTOmed training system can greatly improve the limb function, balance ability, walking ability and self-care ability, reduce muscle tension, and increase nerve growth factor level in older adult patients with post-stroke hemiplegia, which are conducive to the rehabilitation and prognosis of post-stroke hemiplegia.

Effect of neural therapy on NGF and BDNF serum levels in patients with chronic pain. A pilot study / Efecto de la terapia neural sobre los niveles séricos del NGF y el BDNF en pacientes con dolor crónico. Estudio piloto

Abstract Introduction: Neurotrophins (NT) are a family of proteins consisting of the nerve growth factor (NGF), the brain-derived neurotrophic factor (BDNF) and NT-3 and NT-4/5. These proteins play an essential role in neuronal survival, differentiation, and proliferation. Objectives: To analyze the variations of NGF and BDNF serum levels in patients with chronic pain after undergoing neural therapy and to establish the effects of this type of intervention on their quality of life. Materials and methods: Prospective pilot study conducted in 10 patients with chronic pain treated with neural therapy between July 2017 and April 2018 in Bogotá D.C., Colombia. Three consultations were performed (one in which the intervention was initiated, and two follow-up visits every three weeks). During each consultation, the patients' quality of life was assessed using the SF-12 scale and their NGF and BDNF serum levels were measured. Data were analyzed by means of descriptive statistics, using medians and interquartile ranges for quantitative variables, and absolute frequencies and percentages for qualitative variables. Results: The median score on the SF-12 scale tended to improve in the first and second follow-up visits compared with the baseline score (pre-intervention), particularly during the first follow-up visit (consultation No. 1: 34.5; follow-up No. 1: 39.5, and follow-up No. 2: 38). Median NGF serum levels had a downward trend after the intervention, particularly in the first follow-up visit (157.6, 42.95, and 237.8, respectively), and in the case of BNDF, an overall downward trend was also found (29.96, 19.24 and 20.43, respectively). An improvement in quality of life related to the decrease in the serum levels of both neurotrophins was observed. Conclusion: Neural therapy intervention reduced NGF and BDNF serum levels and improved the quality of life of the participants. Therefore, the behavior of these neurotrophins could become a biomarker for the diagnosis, treatment, and follow-up of patients with chronic pain.

Resumen Introducción. Las neurotrofinas (NT) son una familia de proteínas conformada por el factor de crecimiento nervioso (NGF), el factor neurotrófico derivado del cerebro (BDNF) y las neurotrofinas NT-3 y NT-4/5; estas proteínas tienen un papel esencial en la supervivencia, diferenciación y proliferación neuronal. Objetivos. Analizar las variaciones de los niveles séricos del NGF y el BDNF en pacientes con dolor crónico luego de recibir terapia neural y establecer los efectos de este tipo de intervención en su calidad de vida. Materiales y métodos. Estudio piloto prospectivo realizado en 10 pacientes con dolor crónico tratados con terapia neural entre julio de 2017 y abril de 2018 en Bogotá D.C., Colombia. Se realizaron 3 consultas (una en la que se inició la intervención y dos de control cada tres semanas) y en cada una se evaluó la calidad de vida mediante el cuestionario de salud SF-12 y se midieron los niveles séricos del NGF y el BDNF. Los datos se analizaron mediante estadística descriptiva, utilizando medianas y rangos intercuartiles para las variables cuantitativas, y frecuencias absolutas y porcentajes para las cualitativas. Resultados. La mediana de puntaje del cuestionario SF-12 tendió a mejorar en el primer y segundo control comparada con la puntuación inicial (antes de la intervención), en particular en el primer control (consulta 1: 34.5; control 1: 39.5, y control 2: 38). La mediana de los niveles séricos del NGF tendió a disminuir luego de la intervención, en particular en el primer control (157.6, 42.95 y 62.2, respectivamente), y en el caso del BNDF, la tendencia global también fue hacia la disminución (29.96, 19.24 y 20.43, respectivamente). Se observó una mejora en la calidad de vida relacionada con la disminución de los niveles séricos de ambas neurotrofinas. Conclusión. La intervención de terapia neural produjo una reducción en los niveles séricos del NGF y el BDNF y mejoró la calidad de vida de los participantes; por tanto, el comportamiento de estas neurotro-finas podría convertirse en un biomarcador para el diagnóstico, tratamiento y seguimiento de pacientes con dolor crónico.

Níveis Séricos do BDNF na Proteção Cardiovascular e em Resposta ao Exercício / Serum Levels of BDNF in Cardiovascular Protection and in Response to Exercise

Resumo As doenças cardiovasculares (DCV) são atualmente a maior causa de morte no Brasil e no mundo. Em 2016 as DCV foram responsáveis por mais de 17 milhões de mortes, representando 31% de todas as mortes em nível global. Mecanismos moleculares e genéticos podem estar envolvidos na proteção cardiovascular e devem ser considerados nas novas abordagens terapêuticas. Nesse sentido, recentes estudos têm relatado que o Fator Neurotrófico Derivado do Encéfalo (Brain-Derived Neurotrophic Factor, BDNF) está reduzido em indivíduos predispostos a desenvolverem DCV, e que o treinamento físico aeróbio aumenta as quantidades de BDNF circulante. O BDNF é uma neurotrofina encontrada em altas concentrações no hipocampo e córtex cerebral, sendo considerada molécula-chave na manutenção da plasticidade sináptica e na sobrevivência das células neuronais. Além da plasticidade neuronal, BDNF também é importante na função vascular, promovendo angiogênese por meio da regulação por espécies reativas de oxigênio (ROS). Entretanto, uma variante do gene do BDNF em humanos, o polimorfismo Val66Met (substituição do aminoácido valina por uma metionina na posição 66 do códon), que ocorre em 20-30% da população caucasiana, pode afetar as concentrações de BDNF no plasma e sua atividade em todos os tecidos periféricos contendo receptores tirosina quinase B (TrkB), como o endotélio. De fato, recentemente observamos que o polimorfismo Val66Met prejudica a reatividade vascular e o BDNF circulante em resposta ao treinamento físico. Dessa forma, apresentaremos a seguir uma discussão sobre os níveis séricos de BDNF na proteção cardiovascular, a variante genética Val66Met na reatividade vascular e o efeito do exercício físico.

Abstract Cardiovascular disease (CVD) is currently the leading cause of death in Brazil and worldwide. In 2016, CVD accounted for more than 17 million deaths, representing 31% of all deaths globally. Molecular and genetic mechanisms may be involved in vascular protection and should be considered in new therapeutic approaches. In this sense, recent studies have reported that brain-derived neurotrophic factor (BDNF) is reduced in individuals predisposed to develop CVD, and that aerobic physical training increases the amounts of circulating BDNF. BDNF is a neurotrophin found at high concentrations in the hippocampus and cerebral cortex and is considered a key molecule for the maintenance of synaptic plasticity and survival of neuronal cells. In addition to neuronal plasticity, BDNF is also important in vascular function, promoting angiogenesis through the regulation of reactive oxygen species (ROS). However, a variant of the BDNF gene in humans, the Val66Met polymorphism (substitution of the amino acid valine for a methionine at position 66 of the codon), occurring in 20-30% of the Caucasian population, may affect plasma BDNF concentrations and its activity in all peripheral tissues containing tyrosine kinase B receptors (TrkB), such as the endothelium. Thus, we will present a discussion about the role of serum BDNF levels in cardiovascular protection, Val66Met genetic variant in vascular reactivity and the effect of physical exercise.

Expressão de neurotrofinas e de seus receptores no osteossarcoma primário / Expression of neurotrophins and their receptors in primary osteosarcoma

RESUMO Objetivo: determinar a expressão de neurotrofinas e seus receptores tirosina quinases em pacientes com osteossarcoma (OS) e sua correlação com desfechos clínicos. Métodos: biópsias de tumores primários de pacientes com OS tratados em uma única instituição, consecutivamente, entre 2002 e 2015, foram analisados através de imuno-histoquímica para expressão de receptores de tirosina quinase A e B (TrKA e TrKB), fator de crescimento neural (NGF) e fator neurotrófico derivado do cérebro (BDNF). De forma independente, dois patologistas classificaram os marcadores de imuno-histoquímica como negativos (negativos e focais fracos) ou positivos (moderado focal/difuso ou forte focal/difuso). Resultados: foram analisados dados de 19 pacientes (10 do sexo feminino e 9 do masculino) com mediana de idade de 12 anos (5 a 17,3 anos). Dos tumores, 83,3% estavam localizados em membros inferiores e 63,2% dos pacientes eram metastáticos ao diagnóstico. A sobrevida global em cinco anos foi de 55,3%. BDNF foi positivo em 16 pacientes (84%) e NGF em 14 pacientes (73%). TrKA e TrKB apresentaram coloração positiva em quatro (21,1%) e oito (42,1%) pacientes, respectivamente. A análise de sobrevida não demonstrou diferença significativa entre receptores TrK e neurotrofinas. Conclusão: amostras de OS primário expressam neurotrofinas e receptores TrK através de imuno-histoquímica. Estudos futuros podem auxiliar na identificação do papel das mesmas na patogênese do OS e determinar se há possível correlação prognóstica.

ABSTRACT Objective: to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes. Methods: we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse). Results: we analyzed data from 19 patients (10 females and 9 males), with median age of 12 years (5 to 17.3). Tumors' location were 83.3% in the lower limbs, and 63.2% of patients had metastases at diagnosis. Five-year overall survival was 55.3%. BDNF was positive in 16 patients (84%) and NGF in 14 (73%). TrKA and TrKB presented positive staining in four (21,1%) and eight (42,1%) patients, respectively. Survival analysis showed no significant difference between TrK receptors and neurotrophins. Conclusion: primary OS samples express neurotrophins and TrK receptors by immunohistochemistry. Future studies should explore their role in OS pathogenesis and determine their prognostic significance in larger cohorts.

The effect of injecting mouse nerve growth factor on the recovery of hand function in patients with cubital tunnel syndrome / 中华物理医学与康复杂志

Objective To observe the effectiveness of injecting mouse nerve growth factor ( mNGF) on the recovery of hand motor function among patients with cubital tunnel syndrome. Methods A total of 138 patients with moderate to severe cubital tunnel syndrome were randomly divided into groups designated as A, B and C, each of 46. Twenty micrograms of mNGF was injected daily 1 mm from the ulnar nerve at the cubital tunnel for the patients of group A and the injection site was moved 1 mm distally everyday along the nerve , but injected intramuscularly for those in group B. Those in group C received 500 μg of mecobalamin injected intramuscularly 3 times a week. The whole intervention consisted of two 4-week phases, with an interval of 2 months. Before and after the intervention, the function of internal hand muscles, hand function recovery rates and any electrophysiological changes in the ulnar nerve were measured and compared between the two groups. Results All of the patients showed significant improve-ment in hand muscle function and neuroelectrophysiology. The incidence of had muscle atrophy, Tinel′s sign, posi-tiveness in the paper clamping test and claw hand all significantly improved compared with before the treatment in all three groups. The average Disability of Arm Shoulder and Hand score in group A after the treatment was significantly higher than the group B and group C averages. The average ulnar nerve conduction velocity, incubation period and amplitude of group A after the treatment were all significantly better than before the treatment and better than the other groups′averages. After the treatment, the average hand function recovery in group A reached 91％, significantly high-er than in groups B ( 76％) and C ( 59％) . Conclusion Injecting mNGF next to the ulnar nerve is superior to in-jecting it intramuscularly in promoting the recovery of the ulnar nerve and hand function for patients with moderate to severe cubital tunnel syndrome.

The role of neuropsychiatric factors in the occurrence of psoriasis / 中华皮肤科杂志

Considerable evidence has indicated that psychological factors,such as anxiety,nervousness and mental stress,can induce or exacerbate psoriasis and affect therapeutic effects to a certain degree,suggesting that psychological factors may play an important role in the occurrence of psoriasis.Current researches on neuropsychiatry-related pathogenesis of psoriasis mainly include two aspects:on the one hand,acting as stressors,psychological factors can activate the following two neuroendocrine systems,including hypothalamic-pituitary-adrenocortical axis and sympathetic-adrenal medullary system;on the other hand,neuropeptides and nerve growth factors induce in vivo neurogenic inflammation.Neuropsychiatric factors may participate in the occurrence of psoriasis through the above pathways.

Stem cell therapy in pain medicine / 대한통증학회지

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.

Circulating levels of neurotrophic factors are unchanged in patients with Parkinson's disease / Os níveis circulantes de fatores neurotróficos não estão alterados em pacientes com doença de Parkinson

ABSTRACT There is great evidence linking neurotrophic factor (NF) dysfunction with Parkinson's disease (PD) pathophysiology. This study was conducted to evaluate plasma levels of NFs and their possible associations with clinical symptoms in PD. For this purpose, 40 PD patients and 25 controls were subjected to a clinical evaluation and peripheral blood draw. Plasma levels of brain-derived neurotrophic factor (BDNF), pro-BDNF, neurotrophin 3, neurotrophin 4, nerve growth, glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were measured by enzyme-linked immunosorbent assay. There was no significant difference between PD patients and controls regarding the plasma levels of the evaluated NFs. In addition, NF levels were not associated with disease duration, degree of motor or functional impairment, cognitive performance or severity of depressive symptoms. In conclusion, although NFs may play relevant roles in the pathophysiology of PD, the circulating levels of these molecules are not necessarily changed in patients with PD.

RESUMO Há evidências de que alteracões nas ações exercidas por fatores neurotróficos (FNs) estejam associadas à fisiopatologia da doença de Parkinson (DP). O presente estudo foi conduzido para avaliar os níveis plasmáticos de FNs e suas possíveis associações com sintomas clínicos na DP. Para este fim, 40 pacientes com DP e 25 controles foram submetidos à avaliação clínica e coleta de sangue periférico. Os níveis plasmáticos do fator neurotrófico derivado do cérebro (BDNF), pro-BDNF, neurotrofina 3, neurotrofina 4, fator de crescimento do nervo, fator neurotrófico derivado da glia e fator neurotrófico ciliar foram avaliados por ensaio de imunoadsorção enzimática. Não houve diferença significativa entre pacientes com DP e controles quanto aos níveis plasmáticos dos FNs avaliados. Além disso, não encontramos associação entre os níveis dos FNs e duração da doença, grau de comprometimento motor ou funcional, desempenho cognitivo e gravidade dos sintomas depressivos. Em conclusão, embora os FNs possam desempenhar papéis relevantes na fisiopatologia da DP, os níveis circulantes dessas moléculas não estão necessariamente alterados em pacientes com DP.

The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury

Abstract Purpose: To investigate the effect of hyperbaric oxygen therapy (HBOT) on traumatic brain injury (TBI) outcome. Methods: The modified Marmarou's weight drop device was used to generate non-lethal moderate TBI rat model, and further developed in vitro astrocytes culturing system. Then, we analyzed the expression changes of interested genes and protein by quantitative PCR and western blot. Results: Multiple HBO treatments significantly reduced the expression of apoptosis promoting genes, such as c-fos, c-jun, Bax and weakened the activation of Caspase-3 in model rats. On the contrary, HBOT alleviated the decrease of anti-apoptosis gene Bcl-2 and promoted the expression of neurotrophic factors (NTFs), such as NGF, BDNF, GDNF and NT-3 in vivo. As a consequent, the neuropathogenesis was remarkably relied with HBOT. Astrocytes from TBI brain or those cultured with 21% O2 density expressed higher NTFs than that of corresponding controls, from sham brain and cultured with 7% O2, respectively. The NTFs expression was the highest in astrocytes form TBI brain and cultured with 21% O2, suggesting a synergistic effect existed between TBI and the following HBO treatment in astrocytes. Conclusion: Our findings provided evidence for the clinical usage of HBO treating brain damages.

Expression of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and the GDNF Family Receptor Alpha Subunit 1 in the Paravaginal Ganglia of Nulliparous and Primiparous Rabbits / 대한배뇨장애요실금학회지

PURPOSE: To evaluate the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptor, GDNF family receptor alpha subunit 1 (GFRα-1) in the pelvic (middle third) vagina and, particularly, in the paravaginal ganglia of nulliparous and primiparous rabbits. METHODS: Chinchilla-breed female rabbits were used. Primiparas were killed on postpartum day 3 and nulliparas upon reaching a similar age. The vaginal tracts were processed for histological analyses or frozen for Western blot assays. We measured the ganglionic area, the Abercrombie-corrected number of paravaginal neurons, the cross-sectional area of the neuronal somata, and the number of satellite glial cells (SGCs) per neuron. The relative expression of both GDNF and GFRα-1 were assessed by Western blotting, and the immunostaining was semiquantitated. Unpaired two-tailed Student t -test or Wilcoxon test was used to identify statistically significant differences (P≤0.05) between the groups. RESULTS: Our findings demonstrated that the ganglionic area, neuronal soma size, Abercrombie-corrected number of neurons, and number of SGCs per neuron were similar in nulliparas and primiparas. The relative expression of both GDNF and GFRα-1 was similar. Immunostaining for both GDNF and GFRα-1 was observed in several vaginal layers, and no differences were detected regarding GDNF and GFRα-1 immunostaining between the 2 groups. In the paravaginal ganglia, the expression of GDNF was increased in neurons, while that of GFRα-1 was augmented in the SGCs of primiparous rabbits. CONCLUSIONS: The present findings suggest an ongoing regenerative process related to the recovery of neuronal soma size in the paravaginal ganglia, in which GDNF and GFRα-1 could be involved in cross-talk between neurons and SGCs.

The effect of netrin-1 on activation of Müller cell in diabetes rats / 中华眼底病杂志

Objective To observe the effect of netrin-1 on retinal Müller cells in diabetes mellitus (DM) rats. Methods Fifty Sprague-Dawley rats were randomly divided into the normal control group (group A), normal + balanced salt solution (BSS) group (group B), normal+netrin-1 group (group C), DM+BSS group (group D) and DM+netrin-1 group (group E), with 10 rats in each group. DM rats were induced by intraperitoneal injection of Streptozotocin (60 mg/kg). The expression level of glial fibrillary acidic protein (GFAP) on retinal Müller cells was determined by immunohistochemistry, the level of GFAP mRNA was analyzed by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Results Immunohistochemistry showed that GFAP was distributed in retinal ganglion cells and retinal nerve fiber layer in group A, B and C. Compared to group B, GFAP staining was brighter in the group D. There were significant differences in the expression of GFAP protein and mRNA among groups A-E (F=203.43, 72.91; P=0.00, 0.00), they were higher in group D than group A (t=-26.01, 22.26; P=0.00, 0.00), and group E (t=-10.78, 3.93; P=0.00, 0.00). They were higher in group E than group A (t=7.00, -9.82; P=0.00,0.00). There were no significant differences in between group A and group C (t=-0.29, 0.50; P=0.77, 0.62). Conclusion The expression of GFAP in Müller cells of DM rats could be decreased by injecting netrin-1 into vitreous.

The effect of netrin-1 on activation of Müller cell in diabetes rats / 中华眼底病杂志

Objective To observe the effect of netrin-1 on retinal Müller cells in diabetes mellitus (DM) rats. Methods Fifty Sprague-Dawley rats were randomly divided into the normal control group (group A), normal + balanced salt solution (BSS) group (group B), normal+netrin-1 group (group C), DM+BSS group (group D) and DM+netrin-1 group (group E), with 10 rats in each group. DM rats were induced by intraperitoneal injection of Streptozotocin (60 mg/kg). The expression level of glial fibrillary acidic protein (GFAP) on retinal Müller cells was determined by immunohistochemistry, the level of GFAP mRNA was analyzed by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Results Immunohistochemistry showed that GFAP was distributed in retinal ganglion cells and retinal nerve fiber layer in group A, B and C. Compared to group B, GFAP staining was brighter in the group D. There were significant differences in the expression of GFAP protein and mRNA among groups A-E (F=203.43, 72.91; P=0.00, 0.00), they were higher in group D than group A (t=-26.01, 22.26; P=0.00, 0.00), and group E (t=-10.78, 3.93; P=0.00, 0.00). They were higher in group E than group A (t=7.00, -9.82; P=0.00,0.00). There were no significant differences in between group A and group C (t=-0.29, 0.50; P=0.77, 0.62). Conclusion The expression of GFAP in Müller cells of DM rats could be decreased by injecting netrin-1 into vitreous.

The effect of netrin-1 on the retinal vascular permeability in diabetes mellitus rats / 中华眼底病杂志

Objective To observe the effect of different concentration netrin-1 on retinal vascular permeability in diabetes mellitus (DM) rats.Methods Eighty adult Sprague-Dawley rats were randomly divided into 8 groups,10 rats in each group,including normal control group (group A),normal+balanced salt solution (BSS) group (group B),normal+netrin-1 (500 μg/ml) group (group C) and DM group (50 rats in 5 subgroups).DM rats were induced by intraperitoneal injection of streptozocin.Three months after intraperitoneal injection,10 DM rats in the control group were injected with BSS (group D).Forty DM rats were injected with 5 μl of different concentrate netrin-1,and were divided into DM+netrin-1 10 μg/ml group (group E),DM+netrin-1 50 μg/ml group (group F),DM+netrin-1 100 μg/ml group (group G),DM+netrin-1 500 μg/ml group (group H)according to the different concentration.Non-DM rats in group C were injected with netrin-1 500 μg/ml.The expression of occludin was determined by immunohistochemistry for protein,and by real-time fluorescence quantitative reverse transcription polymerase chain reaction for mRNA level.Retinal vascular permeability was measured by Evans blue infusion.Results The expression of occludin protein and mRNA in group D were less than group A (t=27.71,8.59;P=0.00,0.00).However,the retinal vascular permeability increased in group D (t=-42.72,P=0.00).The expression of occluding protein,occludin mRNA and retinal vascular permeability showed significant differences between group D,E,F,G and H (F=146.31,16.54,67.77;P=0.00,0.00,0.00).Compared the group B with group C,there was no significant differences between the expression of occludin protein,occludin mRNA and the retinal vascular permeability (t=-1.13,0.93,1.04;P=0.27,0.36,0.31).The concentrate of netrin-1 showed a significant positive correlation to the expression level of occludin and occludin mRNA (r=0.73,0.81;P=0.00,0.00),but negative correlation to the vascular permeability (r=-0.61,P=0.00).Conclusion Netrin-1 can reduce the DM rats' retinal vascular permeability,which depended on the concentration of netrin-1.

Nerve growth factor injections administered intranasally combined with exercise can improve learning and memory / 中华物理医学与康复杂志

Objective To investigate the effect of nerve growth factor ( NGF) combined with exercise train-ing on nerve protection, learning and memory. Methods Twenty-four six-month-old APP/PS1 mice were randomly divided into a control group, an NGF group, an exercise group and an NGF combined with exercise training group ( the combined group) , each of 6. The control group mice were given 50 μL of saline intra-nasally every day, while the NGF group were given 50 μL of NGF solution (0.1 mg/ml) intranasally. The exercise group was given 50μL of saline intra-nasally plus 30 minutes of treadmill exercise daily, while the combined group was given 50μL of the NGF solution and 30 minutes of exercise. The intervention lasted 21 days. Then Morris water maze test was conducted to e-valuate the memory of all groups, and all of the mice were sacrificed and immunohistochemical staining was used to check the levels of APP, Ki-67 expression in cortex and NeuN expression in hippocampus. Results In the place navigation test, significant differences in escape latency were observed among the 4 groups, with the NGF, exercise and combined groups showing average latencies significantly shorter than that of the control group The average latency of the combined group was also significantly shorter than that of the NGF and exercise groups. In the spatial probe, there were significant differences among the 4 groups in the percentage of time spent in the target quadrant. The com-bined group′s average was significantly larger than those of the NGF and exercises groups. The immunochemistry showed that the combined group had better-arranged neurons and more cells compared with the 3 other groups. The average APP protein expression of the combined group was significantly lower than that of the other groups, but their Ki-67-positive and NeuN-positive cells were found to be significantly more numerous. Conclusion NGF combined with exercise can improve learning and memory, at least in APP/ PS1 mice. This might be associated with its reduc-ing the expression of APP and promoting the expression of Ki-67 and NeuN.

Mouse nerve growth factor for treating dysphagia induced by radiotherapy in patients with nasopharyngeal carcinoma / 中华物理医学与康复杂志

Objective To evaluate the effectiveness and safety of mouse nerve growth factor in treating dysphagia in patients with nasopharyngeal carcinoma after radiotherapy.Methods Fifty-eight post-radiotherapy nasopharyngeal carcinoma patients with dysphagia were randomly divided into an observation group and a control group.Both groups received routine treatment,but the observation group was additionally injected with mouse nerve growth factor intramuscularly every day for four weeks.Before and after the 4 weeks of treatment,both groups were evaluated using Kubota's water drinking test,videofluoroscopy and the brief version of the WHO's Quality of Life scale.Results After 4 weeks,the patients in the observation group displayed significantly greater improvement in swallowing compared with the control group.There was a significant difference in the groups' average scores on the drinking water test and in the videofluoroscopy results.Moreover,the patients in the observation group had significantly higher quality of life scores than those in the control group,on average.Conclusions Mouse nerve growth factor may have a rapid and safe therapeutic effect on dysphagia induced by radiation.No obvious adverse reactions were observed.

The effects of the bone marrow mesenchymal stem cells on the expression of neurotrophic factor protein gene in rabbits with retinal detachment / 中华眼底病杂志

Objective To observe the effects of the bone marrow mesenchymal stem cells (BMSCs) on the expression of neurotrophic factor protein gene in the retinal detachment (RD) rabbits.Methods 60 healthy rabbits were randomly divided into control group (group A),retinal detachment with PBS group (group B),retinal detachment with BMSCs group (group C),20 rabbits in each group.RD model were established for rabbits in group B and C.10 μl PBS was injected into the subretinal space of rabbits in group B,while 10 μl CM-Dil labeled BMSC PBS was injected into subretinal space of rabbits in group C.The rabbits in the group A received no treatment.At 1,2 and 4 weeks after modeling,the mRNA expression of basic fibroblast growth factor (bFGF),brain derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) were measured by real-time quantitative PCR.Results At 1,2 and 4 weeks after modeling,the mRNA expression of bFGF,BDNF,CNTF on retinal tissue were increased significantly in group C as compared with group A and B (P＜0.01).At 1 week after modeling,the mRNA expression of bFGF and CNTF on retinal tissue were increased significantly in group B as compared with group A,the mRNA expression of BDNF on retinal tissue in group B was similar with group C.At 2 and 4 weeks after modeling,the mRNA expression of bFGF,BDNF,CNTF were decreased in group B as compared with group A.Conclusion Subretinal transplantation of BMSC can increase the mRNA expression of bFGF,BDNF and CNTF on retinal tissue in RD rabbits.

Brain-derived neurotrophic factor in the development and metabolism of bone and tooth：promoting or inhibiting proliferation and differentiation? / 中国组织工程研究

BACKGROUND:Brain-derived neurotrophic factor has been detected in bone and tooth, and its role in development and metabolism of bone and tooth tissue as wel as its clinical application has become a hot spot. OBJECTIVE: To summarize and analyze the effect and mechanism of brain-derived neurotrophic factor in development and metabolism of bone and tooth tissues. METHODS: Papers addressing the effect of brain-derived neurotrophic factor in bone and tooth tissue were retrieved by computer in Wanfang and PubMed databases with the key words of “brain-derived neurotrophic factor, TrkB, p75NTR, signaling, bone, tooth, osteoblasts, osteoclasts” in Chinese and English, respectively. A total of 53 papers were included for review. RESULTS AND CONCLUSION:Brain-derived neurotrophic factor can be detected in various tissuesin vivo, and can regulate cel survival and apoptosis through binding its two receptors. Brain-derived neurotrophic factor in bone and tooth tissue can bind to target cels, induce or inhibit cel proliferation and differentiation, indicating that brain-derived neurotrophic factor is closely linked to bone and tooth tissue, and may play a role in growth and reconstruction of bone and tooth. Its mechanism of action is mainly through binding to TrkB receptor, to activate downstream pathways and affect differentiation and proliferation of mesenchymal stem cels, osteoblasts, chondrocytes, and periodontal ligament cels. Interaction between p75NTR receptor and TrkB receptor may be one of the factors affecting cel differentiation or proliferation.

Clinical observation of the effect of mouse nerve growth factor on anterior ischemic optic neuropathy / 天津医药

Objective To observe curative effect of the rat nerve growth factor (NGF) treatment on anterior ischemic op?tic neuropathy(AION). Methods Patients with AION (n=78) were randomly divided into mouse NGF treatment group (treatment group):39 cases (39 eyes) and conventional treatment group (control group):37 cases (37 eyes). Patients in control group were given Actovegin 1.2 g intravenously, once a day while patients in treatment group were given 18μg mouse NGF once a day. Milton insurable were given orally at 0.5 mg, 3 times per day at both groups. Dexamethasone of 3 mg were given retrobulbarly once a day upon onset of symptoms and the extend of edema for 3 to 5 days. Rat nerve growth factor were given for consecutive14 days as a period of treatment, and the curative effect was observed after 28 days of treatment. Results In the treatment group:treatments were obviously effective in 28 eyes (71.79%), effective in 7 eyes (17.95%) and ineffective in 4 eyes (10.26%), so the total effective rate was 89.74%; In control group: treatments were obviously effective in 11 eyes (29.73%), effective in 15 eyes (40.54%) and ineffective in 11 eyes (29.73%), so the total effective rate was 70.27%. Curative effects in these 2 groups were of statistical significance (Z=3.552, P<0.05). Vision acuity and average light sensitivity in vi?sual field are better in treatment group than those control group (P<0.05). Conclusion Mouse NGF is effective in the treat?ment of AION and can improve vision acuity and visual field, therefore is worth promoting.

A neurotoxicidade da Cannabis sativa e suas repercussões sobre a morfologia do tecido cerebral / Cannabis sativa neurotoxicity and impacts on the brain tissue morphology

Para a compreensão das repercussões psicológicas e comportamentais verificadas em usuários de Cannabis sativa, experimentos têm sido desenvolvidos analisando a relação entre a intensidade do uso da droga e biomarcadores de lesão e inflamação. Dessa forma, este estudo teve como objetivo realizar pesquisa bibliográfica, relacionando marcadores bioquímicos de neurotoxicidade e suas repercussões sobre a morfologia do tecido cerebral em usuários de Cannabis sativa, durante a exposição ao Δ9-THC por via intravenosa e em pesquisas in vitro. Trata-se de uma revisão narrativa cuja pesquisa bibliográfica foi realizada nos bancos de dados PubMed, SciELO e Google Acadêmico, utilizando-se como critério de inclusão os seguintes termos: "Cannabis Sativa", "marijuana", "maconha", "Δ9-THC", "neurotrophins", "neurotrofinas", "prostaglandins", "prostaglandinas", "BDNF" e "NGF". Dessa forma, foram selecionados 40 artigos para integrar a presente revisão, datados de 1987 a 2013. O período de realização da pesquisa bibliográfica foi de agosto de 2011 a maio de 2013. Foi possível identificar os tipos e a magnitude das alterações morfológicas e bioquímicas decorrentes do uso de Cannabis sativa ou da exposição ao Δ9-THC. De uma forma geral, foi constatada a diminuição das massas cinzenta e branca do cérebro, da densidade do hipocampo, do volume das células neurais, entre outros. Foram constatadas também alterações nos níveis séricos de neurotrofinas e na biossíntese de prostaglandinas, de acordo com a metodologia utilizada ou região avaliada. Esses achados poderiam estar relacionados às mudanças comportamentais observadas em usuários de Cannabis sativa, esclarecendo, por exemplo, diversos sintomas psíquicos relatados na literatura.

In order to understand psychological and behavioral impact among Cannabis sativa users, experiments have been developed by analyzing the relationship between the intensity of the use with injury and inflammation biomarkers. Therefore, this paper aimed to carry out a literature review, relating biochemical markers of neurotoxicity and their impact on morphology of brain tissue in Cannabis sativa users, during the exposure to Δ9-THC intravenously and in in vitro studies. This is a narrative review whose bibliographic research was managed in PubMed, SciELO and Google Scholar databases, using the following terms as inclusion criterion: "Cannabis sativa", "marijuana", "maconha", "Δ9-THC", "neurotrophins", "neurotrofinas", "prostaglandins", "prostaglandinas", "BDNF" and "NGF". Thereby, 40 articles were selected to integrate the present review, dated from 1987 to 2013. The period of this literature review was from August 2011 to May 2013. It was possible to identify the types and the magnitude of morphological and biochemical changes resulting from the Cannabis sativa use or exposure to Δ9-THC. In general, a reduction was found in gray and white brain mass, in density of hippocampus, in the volume of nerve cells, among others. We also observed changes in serum levels of neurotrophins and in prostaglandin biosynthesis, in accordance with methodology used or the evaluated area. These findings could be related to behavioral changes observed in Cannabis sativa users, clarifying, for instance, many psychological symptoms reported in literature.