Glia function in the endocanabinoid system: narrative review / Função da glia no sistema endocanabinoide: revisão narrativa

ABSTRACT BACKGROUND AND OBJECTIVES: Evidence has highlighted a role of glial cell activation, and their interaction with different neural systems, especially the endocannabinoid system, in the mechanisms involved in the chronicity and maintenance of pain. The aim of this review is to bring an update on published data that demonstrate the interaction between glial cells and the endocannabinoid system in the pathophysiology of chronic pain and its treatment. CONTENTS: A narrative review was performed based on a research in the Medline database, using the Keywords "endocannabinoid", "glial cells", "microglial", "astrocytes", "neuroinflammation". CONCLUSION: Deepening the knowledge about the function of glial cells in the endocannabinoid system will open the possibility of acting on the pathophysiological origin of the pain chronification process, attenuating the mechanisms involved in central sensitization.

RESUMO JUSTIFICATIVA E OBJETIVOS: A evidência científica tem ressaltado um papel da ativação das células da glia e de sua interação com diversos sistemas neurais, com destaque para o sistema endocanabinoide e mecanismos envolvidos na cronificação e manutenção da dor. O objetivo deste estudo foi atualizar os dados publicados que mostrem a interação entre as células da glia com o sistema endocanabinoide na fisiopatologia da dor crônica e seu tratamento. CONTEÚDO: Foi realizada uma revisão narrativa baseada em pesquisa na base de dados Medline, com uso dos unitermos "endocannabinoid", "glial cells", "microglial", "astrocytes", "neuroinflammation". CONCLUSÃO: O aprofundamento do conhecimento acerca da função das células da glia no sistema endocanabinoide abrirá a possibilidade de atuação sobre a origem fisiopatológica do processo de cronificação de dor, atenuando os mecanismos envolvidos na sensibilização central.

Acupuncture intervening depressive disorder:research progress in its neurobiological mechanism / 针灸推拿医学（英文版）

Depressive disorder seriously affects people's physical and mental health.Acupuncture is a safe and effective treatment for depression,yet,its mechanism is unclear.Therefore,acupuncture's action mechanism in intervening depression was summarized from several perspectives,including morphology and ultrastructure of neurons in depression-related brain areas,function and structure of glial cells,brain functional and structural connectivity,and neuroelectrophysiology.It's discovered that acupuncture can repair the morphological and ultrastructural damage of neurons in the hippocampus and prefrontal lobe,mitigate the functional and structural injuries of glial cells in the hippocampus and prefrontal lobe,strengthen functional connectivity and heal structural connection,and promote neuroelectrophysiological activities,which possibly are the principal mechanisms of how acupuncture works in intervening depressive disorder.

Electrical stimulation of the posterior insular cortex induces opioid and cannabinoid-dependent antinociception and regulates glial cells in the spinal cord / A estimulação elétrica do córtex insular posterior induz antinocicepção opioide e canabinoide dependente e regula células da glia na medula espinal

ABSTRACT BACKGROUND AND OBJECTIVES: Half of neuropathic pain patients still end up failing clinical treatments. Electrical stimulation of the posterior insular cortex (ESI) modulates sensory and nociceptive circuits. This study evaluated the effects of a range of frequencies of ESI proposed to improve neuropathic pain. METHODS: Male Sprague Dawley rats, 280-340 g, submitted to the chronic constriction of the right sciatic nerve were tested for mechanical sensitivity using the paw pressure and von Frey flaments tests, and for thermal sensitivity using the hot plate test. The rats were submitted to ESI 10, 60 or 100 Hz (one, five or seven ESI, 15 min, 210 µs, 1V), applied to the posterior insular cortex, and were evaluated in the tests before and after ESI, or in follow-up of 48, 72 and 168h. The open field evaluated general activity after ESI 5. The involvment of opioid and cannabinoid testes were evaluated through treatment with naloxone and SR1416A - antagonist and inverse agonist/antagonist of the receptors, respectively, after ESI 5, while activation of astrocytes, marked by glial fibrillary acid protein (GFAP), and of microglia, marked by IBA-1 (glial marker), in the spinal cord evaluated by immunohistochemistry. RESULTS: Data demonstrate that 10, 60, and 100 Hz ESIs modulate mechanical and thermal sensitivity. ESI 5 increased immunoreactivity of GFAP in the spinal cord, without altering IBA-1 (glial marker). Naloxone and SR141716A reversed the antinociception of 60 Hz ESI 5. 60 Hz ESI 7 induced antinociception up to 72h. CONCLUSION: 60 Hz ESI induces opioid and cannabinoid-dependent antinociception and regulates glia. HIGHLIGHTS 60 Hz-delivered ESI was the best analgesic protocol for the insular stimulation. Data showed a prolonged analgesic effect up to 72h after repetitive ESI. ESI regulates glia activation in pain modulatory system.

RESUMO JUSTIFICATIVA E OBJETIVOS: Metade dos pacientes com dor neuropática são refratários aos tratamentos. A estimulação elétrica do córtex insular (EECI) posterior modula circuitos sensoriais e nociceptivos. Assim, este estudo avaliou os efeitos de uma faixa de frequências de EECI como tratamento em modelo animal de dor neuropática. MÉTODOS: Ratos machos, Sprague Dawley, 280-340 g, submetidos a cirurgia para indução de constrição crônica (ICC) do nervo isquiático direito, foram avaliados em relação à sensibilidade mecânica com a utilização do teste de pressão de pata e de flamentos de von Frey, e sensibilidade térmica usando o teste de placa quente. Os ratos foram submetidos a EECI de 10, 60 ou 100 Hz (uma, cinco ou sete EECI, 15 min, 210 µs, 1V), aplicada ao córtex insular posterior esquerdo, e avaliados nos testes antes e após EECI, ou em follow up de 48, 72 e 168 horas. Por meio do teste de campo aberto, avaliou-se a atividade geral após a EECI5. O envolvimento de receptores opioides e canabinoides foi avaliado por meio da administração de naloxona e SR141716A - antagonista e agonista/antagonista inverso dos receptores, respectivamente - após a EECI 5, enquanto a ativação de astrócitos - marcada por proteína ácida fibrilar glial (GFAP), e de micróglia - marcada por IBA-1 - na medula espinal foi avaliada por imuno-histoquímica. RESULTADOS: Os dados mostraram que EECI em 10, 60 e 100 Hz modulam a sensibilidade mecânica e térmica dos animais. A EECI 5 aumentou a imunorreatividade de GFAP na medula espinhal, sem alterar IBA-1 (marcador glial). Naloxona e SR141716A reverteram a antinocicepção produzida por EECI 5 de 60 Hz. EECI 7 de 60 Hz induziu antinocicepção por até 72 horas. CONCLUSÃO: A EECI 60 Hz produz antinocicepção dependente de opioides e canabinoides e regula a glia. DESTAQUES A EECI de 60 Hz foi o melhor protocolo analgésico para nossa estimulação insular. Os dados mostram um efeito analgésico prolongado de até 72h após repetidas EECI. A EECI regula a ativação da glia no sistema modulatório da dor.

A case of diffuse leptomeningeal glioneuronal tumor resembling meningitis / 中华神经科杂志

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare, low-grade neoplasm, which is newly categorized into the neuronal and mixed neuro-glial tumor in 2016. The most characteristic imaging findings are diffuse leptomeningeal thickening and enhancement with multiple minor cysts. This article described a case with DLGNT mimicking meningitis, whose cystic lesions were not obvious, with swollen multiple lobes cortex, gyri form cortical calcification and enhanced meninges. Meningeal irritation sign repeated attacks and the clinical symptoms gradually improved after steroid pulse therapy. The biopsy and immunohistochemistry staining were diagnosed as DLGNT. The imaging features and clinical data of this case were analyzed to improve the understanding of the disease in clinical practice.

Dysfunction of lymphatic system and early Parkinson′s disease / 中华神经科杂志

Lymphatic system is the transportation way of cerebrospinal fluid and brain interstitial fluid exchange. And this system is a central nervous drainage system which plays an important role in drainaging and discharging of metabolic waste in the brain. The function of this system can be evaluated indirectly by the perivascular space on magnetic resonance imaging. Parkinson′s disease is a common neurodegenerative disorder. It may be helpful to control the progression of the disease if the changes of perivascular space can be dynamically observed in the early or even prodromal stage of the disease. This article reviews the relationship between lymphatic system disfunction and early stage of Parkinson′s disease.

Inalação da fumaça do tabaco provoca alterações histopatológicas no nervo olfatório de ratas / Inhalation of tobacco smoke causes histopathological changes in the olfactory nerve of rats

Introdução: o tabagismo é uma das principais causas evitáveis de mortes no mundo representando um problema de saúde pública. Objetivo: investigar a relação da exposição passiva à fumaça principal do cigarro e as possíveis alterações histomorfométricas das células gliais, arteríolas e da matriz extracelular do nervo olfatório de ratas. Metodologia: trata-se de um estudo experimental, analítico e quantitativo. Vinte ratas randomizadas divididas em dois grupos, controle e tabaco, foram expostas à inalação da fumaça principal do cigarro por 60 dias utilizando dispositivo validado na literatura. Resultados: a exposição à inalação da fumaça principal do cigarro resultou em alterações significativas no grupo tabaco, tais como, elevação nos níveis de cotinina no plasma sanguíneo, aumento na espessura da parede dos vasos sanguíneos, aumento na porcentagem do colágeno total do tecido, diminuição no número total de astrócitos e aumento no número total de micróglias. Conclusão: a exposição à fumaça principal do cigarro resulta em alterações histomorfométricas que poderiam causar alterações funcionais no nervo olfatório como perda sensorial olfativa. Os achados constatados são fortes o suficiente para servir como alerta a toda a população e às autoridades de saúde, no que se refere às leis antifumo, principalmente em ambientes fechados.

Introduction: smoking is one of the main preventable causes of death in the world and represents a worldwide public health problem. Objective: to investigate the relationship of second hand tobacco smoke and possible histomorphometric changes of glial cells, arterioles and extracellular matrix of the olfactory nerve in rats. Methodology: experimental, analytical and quantitative study, twenty wistar animals randomized into two control and tobacco groups, were exposed to inhalation of main cigarette smoke for 60 days using a device validated in the literature. Results: exposure to inhalation of main cigarette smoke resulted in changes in the tobacco group, such as increased levels of cotinine in the blood plasma, increased thickness of the blood vessel wall, increased percentage of total tissue collagen, decreased in the total number of astrocytes and increase in the total number of microglia. Conclusion: exposure to main cigarette smoke results in histomorphometric changes that can cause changes in the olfactory nerve such as sensory olfactory loss. Our findings are strong enough to serve as a warning to the entire population and to health authorities in relation to smokefree laws especially in closed environments.

Rol de la neuroglia en el trastorno del espectro autista / Role of neuroglia in autism spectrum disorder

RESUMEN: El trastorno del espectro autista (TEA) se caracteriza por presentar déficits persistentes en la comunicación y en la interacción social. Además, patrones de comportamiento, intereses o actividades de tipo restrictivo o repetitivo. Su etiología es compleja y heterogenia, y los mecanismos neurobiológicos que dan lugar al fenotipo clínico aún no se conocen por completo. Las investigaciones apuntan a factores genéticos y ambientales que afectan el cerebro en desarrollo. Estos avances coinciden con un aumento en la comprensión de las funciones fisiológicas y el potencial patológico de la neuroglia en el sistema nervioso central (SNC) que llevó a la noción de la contribución fundamental de estas células en el TEA. Así, el objetivo de este artículo fue revisar brevemente los factores de riesgo clave asociados al TEA y luego, explorar la contribución de la neuroglia en este trastorno. Se destaca el rol de los astrocitos, los microglocitos y los oligodendrocitos en el control homeostático del SNC, en la regulación inmunitaria del cerebro y en la mielinización axonal, así como el mal funcionamiento y las alteraciones morfológicas de estas células en los cerebros autistas.

SUMMARY: Autism spectrum disorder (ASD) is characterized by persistent deficits in communication and social interaction, as well as restrictive or repetitive activities or interests. Its etiology is complex and heterogeneous, and the neurobiological mechanisms that give rise to the clinical phenotype are not yet fully understood. Research points to genetic and environmental factors that affect the developing brain. These advances are consistent with an enhanced understanding of the physiological functions and pathological potential of neuroglia in the central nervous system (CNS) which supports the conclusion of the contribution of these cells in ASD. Therefore, the objective of this article was to briefly review the key risk factors associated with ASD and then explore the contribution of glia in this disorder. The role of astrocytes, microgliocytes and oligodendrocytes in the homeostatic control of the CNS in the immune regulation of the brain and in axonal myelination, as well as malfunction and morphological alterations of these cells in autistic brains are emphasized.

El término glía, una tradición conceptual errada: propuesta de cambio por sinneuronas / The term glia, a wrong conceptual tradition: proposal for change for synneurons

RESUMEN: Desde su descubrimiento, las células no neuronales del sistema nervioso recibieron el nombre de glia, palabra de origen griego que significa unión o pegamento, porque se creía que su función era formar una especie de masilla en la que se encuentran inmersas las neuronas. Desde entonces, mediante nuevas técnicas de tinción, se descubrieron otros tipos celulares que fueron catalogados también como glía, que hasta la fecha siguen siendo consideradas como las células de unión o pegamento del tejido nervioso. El objetivo de este artículo es cuestionar el uso inadecuado del término glía y proponer un nuevo término para designar a las células no neuronales. A pesar del enorme conocimiento que actualmente se tiene de estas células y de la gran variedad de funciones que realizan para mantener el correcto funcionamiento de las neuronas y los circuitos nerviosos, aún se les conserva el nombre de glía, un término errado que desdibuja el verdadero papel que cumplen y su importancia para el sistema nervioso. Por lo anterior, se propone el término "sinneuronas", del prefijo griego syn que significa con o junto con, lo que daría a entender que son células que presentan cercanía estructural y funcional con las neuronas.

SUMMARY: Since their discovery, the non-neuronal cells of the nervous system have been called glia, a word of Greek origin that means union or glue, because it was believed that their function was to form a kind of putty, in which neurons are immersed. Thereafter, new cell types discovered by new staining techniques, were also classified as glia, which to this day are still considered as binding cells or glue of nerve tissue. The objective of this paper is to question the inappropriate use of the term glia and to propose a new term to designate non-neuronal cells. Despite the enormous knowledge that is currently available of these cells and the great variety of functions they perform to maintain the proper functioning of neurons and nerve circuits, they still retain the name of glia, an inappropriate name that blurs the true role they play. Therefore, the term "synneuronas" is proposed, from the Greek prefix syn which means with or together with, what would suggest that they are cells that present structural and functional proximity with to neurons.

An Autopsy Proven Case of CSF1R-mutant Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) with Premature Ovarian Failure

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a progressive degenerative white matter disorder caused by mutations in the tyrosine kinase domain of the CSF1R gene. ALSP is often misdiagnosed as other diseases due to its rarity and various clinical presentations such as Parkinsonism, pyramidal signs, cognitive impairment and/or psychiatric symptoms. We describe an autopsy case of ALSP with a CSF1R mutation. A 61-year-old woman presented insidious-onset gait difficulty for 12 years since her age of 49, and premature ovarian failure since her age of 35. At initial hospital visit, brain magnetic resonance imaging revealed hydrocephalus. Initially, Parkinson's syndrome was diagnosed, and she was prescribed L-dopa/carbidopa because of spasticity and rigidity of extremities, which had worsened. Subsequently, severe neuropsychiatric symptoms and cognitive impairment developed and radiologically, features of leukoencephalopathy or leukodystrophy were detected. She showed a down-hill course and died, 12 years after initial diagnosis. At autopsy, the brain showed severe symmetric atrophy of bilateral white matter, paper-thin corpus callosum, thin internal capsule, and marked hydrocephalus. Microscopically, diffuse loss of white matter, relatively preserved subcortical U-fibers, and many eosinophilic bulbous neuroaxonal spheroids were noted, but there was no calcification. Pigmented glia with brown cytoplasmic pigmentation were readily found in the white matter, which were positive for Periodic acid-Schiff, p62, and CD163 stains, but almost negative for CD68. Whole-exome and Sanger sequencing revealed a CSF1R mutation (c.2539G>A, p.Glu847Lys) which was reported in prior one ALSP case. This example demonstrates that ALSP could be associated with premature ovarian failure.

Protective effect of Cordyceps militaris against hydrogen peroxide-induced oxidative stress in vitro

BACKGROUND/OBJECTIVES: Excessive production of reactive oxygen species (ROS) such as hydroxyl (·OH), nitric oxide (NO), and hydrogen peroxide (H2O2) is reported to induce oxidative stress. ROS generated by oxidative stress can potentially damage glial cells in the nervous system. Cordyceps militaris (CM), a kind of natural herb widely found in East Asia. In this study, we investigated the free radical scavenging activity of the CM extract and its neuroprotective effects in H2O2-induced C6 glial cells. MATERIALS/METHODS: The ethanol extract of CM (100–1,000 µg/mL) was used to measure DPPH, ·OH, and NO radical scavenging activities. In addition, hydrogen peroxide (H2O2)-induced C6 glial cells were treated with CM at 0.5–2.5 µg/mL for measurement of cell viability, ROS production, and protein expression resulting from oxidative stress. RESULTS: The CM extract showed high scavenging activities against DPPH, ·OH, and NO radicals at concentration of 1,000 µg/mL. Treatment of CM with H2O2-induced oxidative stress in C6 glial cells significantly increased cell viability, and decreased ROS production. Cyclooxygenase-2 and inducible nitric oxide synthase protein expression was down-regulated in CM-treated groups. In addition, the protein expression level of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular regulated protein kinases (p-ERK) in H2O2-induced C6 glial cells was down-regulated upon CM administration. CONCLUSION: CM exhibited radical scavenging activity and protective effect against H2O2 as indicated by the increased cell viability, decreased ROS production, down-regulation of inflammation-related proteins as well as p-p38, p-JNK, and p-ERK protein levels. Therefore, we suggest that CM could play the protective role from oxidative stress in glial cells.

Nueva teoría sobre la depresión: un equilibrio del ánimo entre el sistema nervioso y el inmunológico, con regulación de la serotonina-quinurenina y el eje hipotálamo-hipófiso-suprarrenal / A new theory of depression based on the serotonin/kynurenine relationship and the hypothalamic-pituitary-adrenal axis

La hipótesis sobre las causas de la depresión basada en la acción de la serotonina y del sistema inmunológico, propone que ciertos tipos de estrés distorsionan la relación entre la actividad del sistema inmunitario innato y la del sistema nervioso central. El estrés causado por una infección o el estrés psicológico excesivo activan receptores de tipo toll, como el TLR-4, el factor de transcripción NF-kB, el inflamasoma NLRP3, así como la secreción de interleucina 1 beta (IL-1ß) e interleucina 6 (IL-6); esto causa, en primer lugar, los síntomas generales de enfermedad que aparecen con cualquier infección, pero también los síntomas característicos de la depresión como disforia y anhedonia. Las evidencias indican que, si el estímulo persiste o se repite en las siguientes 24 horas, se activa la enzima indolamina 2,3-dioxigenasa (IDO) de la vía metabólica de la quinurenina, lo cual incrementa la síntesis del ácido quinolínico y reduce la síntesis de serotonina. El ácido quinolínico activa los receptores de N-metil-D-aspartato (NMDA) en el sistema nervioso central y estimula la secreción de, entre otras, las interleucinas IL-6 e 1L-1ß, las cuales promueven la hiperactividad del eje hipotálamohipófiso-suprarrenal y refuerzan la desviación del metabolismo del triptófano hacia la producción de ácido quinolínico, así como de las interleucinas de la inmunidad innata, con lo cual se reduce más la síntesis de serotonina y se consolida el proceso depresivo. Este proceso puede ser iniciado por las interleucinas estimuladas por una infección, así como por algunas vacunas o por un estrés psicológico excesivo que active el eje hipotálamo-hipófiso-suprarrenal simultáneamente con la respuesta inmunológica innata, con lo que se provocaría un proceso de inflamación estéril en el sistema nervioso central.

The serotonergic and immunological hypothesis of depression proposes that certain types of excessive stress distort the relationship between the activities of the innate immune and central nervous systems, so that the stress caused by an infection, or excessive psychological stress, activate toll-like receptors such as the TLR-4, the transcription factor NF-kB, the inflammasome NLRP3, as well as the secretion of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and other factors of the innate immune response, causing first, the general symptoms of the disease which appear with any infection, but also those characteristic of depressive illness such as dysphoria and anhedonia. The evidence indicates that, if the stimulus persists or recurs within 24 hours, the indole-2, 3-dioxygenase enzyme (IDO) of the kynurenine metabolic pathway, which increases the synthesis of quinolinic acid, is activated with an associated reduction of serotonin synthesis. Quinolinic acid activates NMDA receptors in the central nervous system and stimulates the secretion of interleukins IL-6 and 1L-1ß, among others, promoting hyper-activity of the HPA axis and reinforcing a bias of the tryptophan metabolism to produce quinolinic acid, and interleukins by the innate immune system, further reducing the synthesis of serotonin and consolidating the depressive process. We discuss the evidence showing that this process can be initiated by either interleukin stimulated by an infection or some vaccines or excessive psychological stress that activates the HPA axis together with said innate immune response, causing a process of aseptic inflammation in the central nervous system.

Role of glial cell in cerebral hemorrhage injury and potential targets for intervention / 中国医师进修杂志

Cerebral hemorrhage is one of the refractory diseases which seriously endangers the safety of human life. Immune and inflammatory reaction participate in the whole process of cerebral hemorrhage, which can destroy the blood-brain barrier, accelerate brain edema, at the same time start and amplify the oxidative stress reaction, and aggravate the nerve function damage. After cerebral hemorrhage, many kinds of signal molecules are produced, which can activate the microglia and astrocytes around the hematoma, produce inflammatory factors and oxidizing mediators, and regulate the inflammatory response of the brain. Exploring the relationship between glial cell and immune, inflammatory responses is helpful to understand the mechanism of intracerebral hemorrhage intervention, find out a new target for the intervention of glial cells and develop new drugs and schemes for the treatment of intracerebral hemorrhage.

Role of talin in activation of astrocytes in spinal cord of rats with diabetic neuropathic pain / 中华麻醉学杂志

Objective To evaluate the role of talin in activation of astrocytes in the spinal cord of rats with diabetic neuropathic pain (DNP).Methods Twenty-four clean-grade healthy male SpragueDawley rats,aged 2-3 months,weighing 180-200 g,were assigned into 3 groups (n =8 each) using a random number table:control group (group C),group DNP and siRNA group (group siR).Rat DNP model was established by injecting streptozotocin (STZ).Group siR received intraspinal injection of siRNA silence stalin at 3 days before injecting STZ,and the equal volume of blank plasmid was given instead in C and DNP groups.The mechanical paw withdrawal threshold (MWT) was measured at 29-35 days after injection of STZ,the rats were then sacrificed and the lumbar spinal cords were removed for determination of the expression of integrin β1 (by Western blot),activation of astrocytes (by immunofluorescence) and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) (using enzyme-linked immunosorbent assay).Results Compared with group C,the MWT was significantly decreased at each time point after surgery,the expression of integrin β1 was up-regulated,and the rate of activated astrocytes and contents of TNF-α and IL-1 were increased in group DNP (P＜0.05).Compared with group DNP,the MWT was significantly increased at each time point after surgery,the expression of integrin β1 was downregulated,and the rate of activated astrocytes and contents of TNF-α and IL-1 were decreased in group siR (P＜0.05).Conclusion Talin is involved in activation of astrocytes in the spinal cord of rats with DNP.

Endogenous protective mechanism of intestinal barrier injury induced by cardiopulmonary bypass in rats: the relationship with enteric glia cells / 中华麻醉学杂志

Objective To evaluate the relationship between endogenous protective mechanism of intestinal barrier injury induced by cardiopulmonary bypass ( CPB) and enteric glia cells in rats. Methods Forty-eight clean-grade adult male Sprague-Dawley rats, weighing 400-500 g, were divided into 2 groups (n=24 each) using a random number table method: sham operation group (group S) and CPB group. Rats were sacrificed at the beginning of CPB, 60 min of CPB, and 2 and 6 h after CPB, and the intestinal tissues were removed for examination of pathological changes ( by HE staining) and for determina-tion of the expression of ZO-1, occludin, glial fibrillary acidic protein ( GFAP ) and calcium-binding pro-tein ( S-100) and the positive expression of GFAP ( by immunohistochemical method) . Results Compared with group S, the expression of GFAP and S-100 was significantly up-regulated at 60 min of CPB and 2 and 6 h after CPB, the expression of ZO-1 and occludin was down-regulated (P<0. 05), the positive expres-sion of GFAP was enhanced, and the intestinal mucosal injury was marked in group CPB. Conclusion The enhanced activation of enteric glia cells may be involved in the endogenous protective mechanism of in-testinal barrier injury induced by CPB in rats.

Early Postnatal Valproic Acid Exposure Increase the Protein Level of Astrocyte Markers in Frontal Cortex of Rat

OBJECTIVE: In our previous study, it has been reported that valproic acid (VPA) effects gliogenesis and increases the number of glial precursor cells during the early postnatal period. However there is no specific report that whether this process is going on up to the age of mature brain development and the consequence effect of this ongoing gliogenesis process. METHODS: As an ongoing study, using Immunoblotting analysis, we checked the level of glial protein and glial-derived factor markers in the frontal cortex of a rat brain at postnatal day (PND) 21. RESULTS: The finding of the study suggests that, in the VPA group (p < 0.05), early exposure elicited significantly to increase the expression level of glial protein cells at PND 21 in the frontal cortex of rat brain. CONCLUSION: Therefore we suggest that, alter gliogenesis and abnormal number of glial cells modulate the neurobiological dysfunction and induces the risk of neurodevelopmental disorders.

MORPHOLOGICAL ADJUSTMENTS OF THE RADIAL NERVE ARE INTENSITY-DEPENDENT / AJUSTES MORFOLÓGICOS DO NERVO RADIAL SÃO DEPENDENTES DE INTENSIDADE / AJUSTES MORFOLÓGICOS DEL NERVIO RADIAL SON DEPENDIENTES DE INTENSIDAD

ABSTRACT Introduction: Peripheral nerve adaptation is critical for strength gains. However, information about intensity effects on nerve morphology is scarce. Objective: To compare the effects of different intensities of resistance training on radial nerve structures. Methods: Rats were divided into three groups: control (GC), training with 50% (GF1) and training 75% (GF2) of the animal’s body weight. The morphological analysis of the nerve was done by light and transmission electron microscopy. One-way ANOVA and the Tukey’s post hoc test were applied and the significance level was set at p≤0.05. Results: Training groups had an increase of strength compared to GC (p≤0.05). All measured nerve components (mean area and diameter of myelin fibers and axons, mean area and thickness of the myelin sheath, and of neurofilaments and microtubules) were higher in GF2 compared to the other (p≤0.05). Conclusion: Results demonstrated greater morphological changes on radial nerve after heavier loads. This can be important for rehabilitation therapies, training, and progression.

RESUMO Introdução: A adaptação dos nervos periféricos é fundamental para ganhos de força. No entanto, as informações relativas aos efeitos da intensidade sobre a morfologia do nervo são escassas. Objetivo: Comparar os efeitos de diferentes intensidades de treinamento de resistência sobre estruturas do nervo radial. Métodos: Os ratos foram divididos em três grupos: controle (GC) e treinamento com 50% (GF1) e 75% (GF2) do peso corporal do animal. A análise morfológica do nervo foi feita com microscopia óptica e eletrônica de transmissão. A one-way ANOVA e o teste post hoc de Tukey foram aplicados e o nível de significância foi estabelecido em p ≤ 0,05. Resultados: Os grupos treinamento tiveram aumento de força com relação ao GC (p ≤ 0,05). Todos os componentes medidos do nervo (área média e diâmetro de fibras de mielina e axônios, área média e espessura da bainha de mielina, neurofilamentos e microtúbulos) foram maiores no GF2 em comparação com os demais (p ≤ 0,05). Conclusão: Os resultados demonstraram maiores alterações morfológicas no nervo radial depois de cargas mais pesadas. Isso pode ser importante para terapias de reabilitação, treinamento e progressão.

RESUMEN Introducción: La adaptación de los nervios periféricos es fundamental para el aumento de fuerza. Sin embargo, la información sobre el efecto de la intensidad sobre la morfología del nervio es escasa. Objetivo: Comparar el efecto de diferentes intensidades de entrenamiento de resistencia en las estructuras del nervio radial. Métodos: Las ratas se dividieron en tres grupos: control (GC) y entrenamiento con 50% (GF1) y con 75% (GF2) del peso corporal del animal. El análisis morfológico del nervio se hizo con microscopía óptica y electrónica de transmisión. Se aplicaron la prueba ANOVA de una vía y la prueba post hoc de Tukey y el nivel de significación se fijó en p ≤ 0,05. Resultados: Los grupos de entrenamiento tuvieron aumento de la fuerza con respecto al grupo control (p ≤ 0,05). Todos los componentes medidos del nervio (área media y diámetro de las fibras de mielina y axones, área media y espesor de la vaina de mielina, neurofilamentos y microtúbulos) fueron mayores en GF2 en comparación con los otros grupos (p ≤ 0,05). Conclusión: Los resultados mostraron mayores cambios morfológicos en el nervio radial después de las cargas más pesadas. Esto puede ser importante para terapias de rehabilitación, entrenamiento y progresión.

Drug discovery for Alzheimer's disease based on the functional disturbance of microglia / 药学学报

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the brain. Due to the uncertain pathogenesis, prevention and treatment of AD is difficult. Clinic symptoms of AD including progressive loss of memory and spatial orientation are rooted in synaptic and neuronal loss. Unsuccessful clinical trials of several candidate drugs based on amyloid hypothesis and tau hypothesis have led to exploration of new approaches. Neuro-inflammation characterized by dysfunction in microglia is believed to be the hallmark of AD and also the initiator of downstream responses in neurodegeneration. Alleviate microglia activation and neuro-inflammation may delay AD development. In this paper, we describe the current literature on interaction between microglia and neuron, and review the progress in AD drug discovery and neuro-inflammatory inhibitors for treatment of AD.

Response of NG2 positive cells and other glial cells in the microenvironment of facial nucleus after facial nerve axotomy / 解放军医学杂志

Objective To study the response of NG2 positive and other glial cells in the facial nucleus after facial nerve axotomy,and explore the changes of the microenvironment in the facial nucleus.Methods Rat facial nerve axotomy models were established.Immunofluorescence double staining,and immunohistochemical staining combined with cresyl violet staining were used to observe the response of NG2 cells and other glial cells,and Western blotting was performed to test NG2 protein expression in facial nucleus at postoperative 1,2,7,14,and 28 days.Results Microglia formed dense circles closely around the injured neurons.Astrocytes formed wreath-like structure near the injured neurons.NG2 protein in the injured nucleus has a regular timephase change and NG2 positive cells showed an extensive detachment of synaptic terminals on the damaged neurons after facial nerve axotomy.NG2 cell response was almost the same as microglia.Conclusions All kinds of glial cells may be involved in the formation of glial scar.NG2 positive cells could insulate the damaged neurons against the potential damage from the excitatory input.

Down syndrome with asymptomatic neuroglial cyst: A case report and review of the literature

Down syndrome (DS, trisomy 21) is associated with neuroanatomical abnormalities, including choroid plexus cysts and various types of brain tumors. Trisomy 21 is associated with oncogenic factor, especially in brain tumor. The brain of DS patients had a smaller volume of gray and white matter and an unbalanced cerebellum volume, indicating a smaller volume overall than normal. We report a case of a DS male patient who had an incidentally discovered neuroglial cyst in left cerebellar vermis. He visited our hospital with gait disturbance and fatigue. But, the neurologic exam was normal. To the best of our knowledge, this is the first reported case of a neuroglial cyst in a trisomy 21 patient. As the developmental mechanisms of a cyst and the choroid plexus are related, more research is needed.

Modified primary culture and identification of human retinal Müller cells / 中华实验眼科杂志

Background Retinal Müller cells are important gliocytcs and the source of retinal stem cells.Researching the biological behavior of Müller cells is of important significance to the study on retinal physiopathological process and stem cell therapy of retinal diseases.To establish a stable culture method of Müller cells is a solid basis of relative basic research.Objective This study was to establish a simple and stable method of isolation and culture of human retinal Müller cells and provide sufficient and high-quality Müller cell source.Methods Human retinal Müller cells were isolated from healthy human donor eyes.The mixture solution of hyaluronidase (100 U) and 0.25％ trypsin were used to digest chopped retinal tissue.The DMEM/F12 medium with 20％ fetal bovine serum (FBS) was added to stop the digestion process.RPMI1640 medium with 20％ FBS was used to culture the cell for 72 hours and then replaced the half medium.The cells were passaged by the RPMI1640 medium with 20％ FBS.The morphology of the cells were examied under the optical microscope,and the expressions of glial fibrillary acidic protein (GFAP),a marker of gliocytes,and glutamine synthetase (GS),a special marker of retinal Müller cells,were detected by immunochemistry and immunofluorescence technology.Results Human retinal Müller cells were successfully isolated by enzyme mixture solution of hyaluronidase (100 U) and O.25％ trypsin.The cells were adherent to walls 24 hours after primary culture and completely merged 9-10 days after culture.The cells showed oval in shape with abundant cytoplasm,and a part of cells presented with cone-shaped bulge bilaterally and ectasia in the posterior containing large nuclei.After cells passage,the cells were enlarged and grew toward polygonal shape.The positive expression of GFAP was observed in more than 95％ cells and strongly positive expression of GS was observed in more than 90％ cells by immunohistochemstry and immunofluorescent staining.Conclusions Human retinal Müller cells can be successfully isolated by hyaluronidase combined with trypsin digestion.Abundent and pure human retinal Müller cells can be obtained by successively using RPMI1640 medium with 20％ FBS and 10％ FBS.