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Introduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis. Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR). Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate. Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score. Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.

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To study the process of neuronal differentiation, the human neuroblastoma (SH-SY5Y) and the murine neuroblastoma (Neuro2a) cell lines have proven to be effective models. For this approach, different protocols involving known neurotrophic factors and other molecules, such as retinoic acid (RA), have been assessed to better understand the neuronal differentiation process. Thus, the goal of this manuscript was to provide a brief overview of recent studies that have used protocols to promote neurodifferentiation in SH-SY5Y and Neuro2a cell lines and used acquired morphology and neuronal markers to validate whether differentiation was effective. The published results supply some guidance regarding the relationship between RA and neurotrophins for SH-SY5Y, as well a serum concentrations for both cell lines. Furthermore, they demonstrate the potential application of Neuro2a, which is critical for future research on neuronal differentiation.

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BACKGROUND: Neurotrophins (NTs) and their precursors (pro-NTs) are polypeptides with important roles in neuronal development, differentiation, growth, survival and plasticity, as well as apoptosis and neuronal death. Imbalance in NT levels were observed in schizophrenia spectrum disorders, but evidence in ultra-high risk for psychosis (UHR) samples is scarce. METHODS: A naturalistic sample of 87 non-help-seeking UHR subjects and 55 healthy controls was drawn from the general population. Blood samples were collected and NT-3, NT-4/5, BDNF, pro-BDNF, NGF, pro-NGF were analyzed through enzyme linked immunosorbent assay (ELISA). Information on cannabis and tobacco use was also collected. Logistic regression models and path analysis were used to control for confounders (tobacco, age, cannabis use). RESULTS: NT-4/5 was significantly decreased, and pro-BDNF was significantly increased in UHR individuals compared to controls. Cannabis use and higher NGF levels were significantly related to transition to psychiatric disorders among UHR subjects. Increased pro-BDNF and decreased NT-4/5 influenced transition by the mediation of perceptual abnormalities. CONCLUSIONS: Our study shows for the first time that NTs are altered in UHR compared to healthy control individuals, and that they can be a predictor of transition to psychiatric illnesses in this population. Future studies should employ larger naturalistic samples to confirm the findings.

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Abstract Rita Levi-Montalcini was a researcher in the field of neuroscience, Italian and Jewish in origin, who discovered the nerve growth factor and rightfully earned the 1986 Nobel Prize in Physiology or Medicine, alongside her collaborator Stanley Cohen. She was persecuted by the fascist dictatorship of Benito Mussolini and experienced gender and religious discrimination throughout her entire life. Despite these obstacles, she carried out her activities with diligence and grace, becoming a role model in the field. This paper reviews the life and career of Rita Levi-Montalcini.

Resumo Rita Levi-Montalcini foi uma pesquisadora no campo das neurociências, de origem Italiana e Judia, que descobriu o fator de crescimento neural e merecidamente recebeu o Prêmio Nobel de Fisiologia ou Medicina de 1986, em conjunto ao seu colaborador Stanley Cohen. Ela foi perseguida pela ditadura fascista de Benito Mussolini, e sofreu discriminação de gênero e religião durante sua vida inteira. A despeito desses obstáculos, sempre exerceu suas atividades com diligência e graça, tornando-se um exemplo nesse campo de estudo. O presente artigo faz uma revisão sobre a vida e carreira de Rita Levi-Montalcini.

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La neuropatía óptica traumática (TON) es una entidad asociada al trauma facial y craneal, y constituye una causa importante para el desarrollo de la ceguera; es una complicación grave del trauma craneofacial que daña directa (dTON) o indirectamente (iTON) el nervio óptico (ON), cuya incidencia global de TON es de 0,7 a 2,5 %. El objetivo del presente estudio es presentar el caso de un paciente que padecía de TON y a la vez de una afección bilateral asimétrica, y que fue tratado con el factor de crecimiento nervioso mNGF. Este medicamento fue el primero que se descubrió y demostró eficacia en mantener la supervivencia de las neuronas centrales y periféricas y facilitar su crecimiento, diferenciación y regeneración. Se trata de un paciente de 13 años, sexo masculino, quien acude a la emergencia del Instituto Nacional de Ciencias Neurológicas y, posteriormente, su seguimiento clínico es por consultorio de Neuroftalmología, con un cuadro de amaurosis traumática, producto de un traumatismo encéfalo craneano con hematoma epidural, que recibió dos ciclos de tratamiento con factor de crecimiento nervioso. Luego del primer ciclo de tratamiento, se evidenció hiporreactividad de ambos ojos; al finalizar el segundo ciclo de tratamiento, se observó un aumento considerable de la agudeza visual. El mNGF está aprobado y comercializado en China desde el año 2015 y es un producto que ha demostrado su eficacia y seguridad en varios ensayos clínicos. Por ello, el presente estudio pretende convertir al factor de crecimiento nervioso como el tratamiento prometedor de iTON; en ese sentido, se necesita de amplias investigaciones clínicas en este caso en particular.

Traumatic optic neuropathy (TON) is an entity associated with facial and cranial trauma, and a leading cause of blindness. It is a severe complication of craniofacial trauma that directly (DTON) or indirectly (ITON) damages the optic nerve (ON) and whose global incidence is 0.7 to 2.5 %. The objective of this study is to present the case of a patient who suffered from TON and, at the same time, an asymmetrical bilateral condition, and was treated with nerve growth factor (NGF). This drug was the first to be discovered and demonstrate efficacy in maintaining the survival of central and peripheral neurons and facilitating their growth, differentiation and regeneration. A 13-year-old male patient attended the emergency room of Instituto Nacional de Ciencias Neurológicas and was later followed up at the Neuro-Ophthalmology Service. He was diagnosed with post-traumatic amaurosis caused by traumatic brain injury and epidural hematoma, and received two treatment cycles of NGF. After the first treatment cycle, hyporeactivity of both eyes occurred. And, at the end of the second treatment cycle, visual acuity improved significantly. NGF has been approved and marketed in China since 2015 and is a product that has demonstrated its efficacy and safety in several clinical trials. Therefore, this study aims to make NGF a promising ITON treatment; in that sense, further clinical research is needed in this particular case.

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Abstract Introduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis. Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR). Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate. Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score. Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.

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PURPOSE: Colorectal cancer (CRC) is one most cancer type of high incidence and high mortality rate. Metastasis play an important role in survival rate and life quality of colorectal cancer patients. Nerve growth factor (NGF) has been shown to be involved in the metastasis and deterioration in many cancers, but the detail mechanisms in promoting the metastasis of colorectal cancer remain unknown. In this study, we aimed to explore the mechanism of NGF promoting colorectal cancer metastasis to provide new insights for developing NGF anti-colorectal cancer drugs. METHODS: We examined the expression of NGF in human colorectal cancer by immunohistochemical staining, and Western blot to evaluate the relationship between NGF and colorectal cancer metastasis. Using biochemical experiments including wound healing assay, transwell migration and invasion assay, RT-PCR, Western blot and ELISA to explore the relative mechanism of NGF promoting colorectal cancer cells metastasis in vivo. RESULTS: Our results found that the high expression of NGF was related with high incidence of metastasis. The binding of NGF to TrkA phosphorylated TrkA, which activated MAPK/Erk signaling pathway increasing the expression NGAL to enhance the activity of MMP2 and MMP9, promoted colorectal cancer metastasis. CONCLUSION: Our finding demonstrated that NGF increased NGAL expression to enhance MMPs activity to promoted colorectal cancer cell metastasis by TrkA-MAPK/Erk axis.

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Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.

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ABSTRACT Background: Stroke is among the leading causes of death and disability worldwide. Interventions for stroke rehabilitation aim to minimize sequelae, promote individuals' independence and potentially recover functional damage. The role of aerobic exercise as a facilitator of post-stroke neuroplasticity in humans is still questionable. Objective: To investigate the impact of aerobic exercise on neuroplasticity in patients with stroke sequelae. Methods: A systematic review of randomized clinical trials and crossover studies was performed, with searches for human studies in the following databases: PUBMED, EMBASE, LILACS and PeDRO, only in English, following the PRISMA protocol. The keywords used for selecting articles were defined based on the PICO strategy. Results: This systematic review evaluated the impacts of aerobic exercise on neuroplasticity through assessment of neural networks and neuronal excitability, neurotrophic factors, or cognitive and functional assessment. Studies that evaluated the effects of aerobic exercise on neuroplasticity after stroke measured through functional resonance (fMRI) or cortical excitability have shown divergent results, but aerobic exercise potentially can modify the neural network, as measured through fMRI. Additionally, aerobic exercise combined with cognitive training improves certain cognitive domains linked to motor learning. Studies that involved analysis of neurotrophic factors to assess neuroplasticity had conflicting results. Conclusions: Physical exercise is a therapeutic intervention in rehabilitation programs that, beyond the known benefits relating to physical conditioning, functionality, mood and cardiovascular health, may also potentiate the neuroplasticity process. Neuroplasticity responses seem more robust in moderate to high-intensity exercise training programs, but dose-response heterogeneity and non-uniform neuroplasticity assessments limit generalizability.

RESUMO Antecedentes: O acidente vascular cerebral (AVC) é a segunda causa principal de morte no mundo. Intervenções para reabilitação dos pacientes com AVC visam minimizar sequelas, promover sua independência e potencialmente recuperar danos funcionais. O papel do exercício aeróbico como facilitador da neuroplasticidade pós-AVC em humanos ainda é questionável. Objetivo: Investigar o impacto do exercício aeróbico na neuroplasticidade em pacientes com sequelas de AVC. Métodos: Foi realizada revisão sistemática de literatura, pesquisando nas seguintes bases de dados: PUBMED, EMBASE, LILACS e PeDRO. Foram selecionados trabalhos em língua inglesa, realizados apenas com humanos, seguindo o protocolo PRISMA. As palavras-chave utilizadas para a seleção de artigos foram definidas com base na estratégia PICO. Resultados: Esta revisão sistemática avaliou os impactos do exercício aeróbico na neuroplasticidade através da avaliação das redes neurais e da excitabilidade neuronal, por meio de fatores neurotróficos, por meio da avaliação cognitiva e funcional. Estudos que avaliaram os efeitos do exercício aeróbico sobre neuroplasticidade após o AVC medido através de ressonância funcional ou excitabilidade cortical, são controversos, mas há dados sugerindo uma modificação da rede neural na ressonância funcional após o exercício aeróbico. Há evidências de que, associar exercício aeróbico com treinamento cognitivo melhora certos domínios cognitivos ligados à aprendizagem motora. Estudos que envolveram a análise de fatores neurotróficos, como avaliação da neuroplasticidade, tiveram resultados conflitantes. Conclusões: Exercício aeróbico é uma intervenção terapêutica em programas de reabilitação, pois, além de proporcionar os benefícios no condicionamento físico, funcionalidade, humor e saúde cardiovascular, pode potencializar a neuroplasticidade.

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ABSTRACT BACKGROUND AND OBJECTIVES: The expression of nerve growth factor (NGF) in the large-size neurons may represent a key role in the neuronal synaptic plasticity and re-organization of neuronal function after a nerve injury. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising tool to pain management since it promotes neuroplasticity in the central system, and it can be combined with other interventions. The aim was to investigate the effects of tDCS in the NGF levels in central and peripheral nervous system structures of rats submitted to a neuropathic pain (NP) model. METHODS: The chronic constriction injury (CCI) of sciatic nerve was used for the induction of NP. For sham surgery, the sciatic nerve was exposed, but without any ligation. The control group did not undergo surgical procedure. After the establishment of NP, treated groups were subjected to tDCS treatment 0.5 mA/20min/day/8 days. NGF levels in cerebral cortex, spinal cord and sciatic nerve were determined by sandwich-ELISA at 48 hours and 7 days after the end of treatment. RESULTS: The CCI model increased NGF levels in all three structures analyzed at long-lasting time, evidencing the importance of this neurotrophin in neuropathic pain condition. On the other hand, there was no tDCS effect in the central and peripheral NGF levels discarding the participation of this neurotrophin in the analgesic tDCS effect. CONCLUSION: tDCS modulation effects of nociceptive pathways seem not to be linked to the NGF signaling in this chronic pain model.

RESUMO JUSTIFICATIVA E OBJETIVOS: A expressão do fator de crescimento neural (NGF) em neurônios de diâmetro largo pode representar um papel importante na plasticidade sináptica neuronal e na reorganização da função neuronal após lesão neural. A estimulação transcraniana por corrente contínua (ETCC) é um método não invasivo de estimulação cerebral e representa uma ferramenta promissora para o manejo da dor, pois promove neuroplasticidade no sistema central, podendo ser combinada com outras intervenções. O objetivo foi investigar os efeitos da ETCC nos níveis de NGF em estruturas do sistema nervoso central e periférico de ratos submetidos a um modelo de dor neuropática (DN). MÉTODOS: A constrição crônica (CCI) do nervo isquiático foi utilizada para indução do modelo de DN. Na cirurgia sham, o nervo foi exposto, no entanto não houve constrição do nervo. O grupo controle não foi submetido ao procedimento cirúrgico. Após estabelecimento da DN, os grupos tratados foram submetidos a ETCC 0,5 mA/20min/dia/8 dias. Os níveis de NGF no córtex cerebral, medula espinal e nervo isquiático foram mensurados pela técnica de ELISA 48 horas e 7 dias após o final do tratamento. RESULTADOS: O modelo de dor CCI aumentou os níveis de NGF nas três estruturas analisadas, evidenciando a importância desta neurotrofina na dor neuropática. Por outro lado, não houve efeito da ETCC nos níveis de NGF central e periférico, descartando o papel desta neurotrofina no efeito analgésico da ETCC. CONCLUSÃO: Efeitos da ETCC sobre vias nociceptivas não estão diretamente relacionados com a sinalização do NGF neste modelo de dor crônica.