Targeting GATA1 and p2x7r Locus Binding in Spinal Astrocytes Suppresses Chronic Visceral Pain by Promoting DNA Demethylation / 神经科学通报·英文版

Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.

Entrainment of Astrocytic and Neuronal Ca2+ Population Dynamics During Information Processing of Working Memory in Mice / 神经科学通报·英文版

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes / 神经科学通报·英文版

Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.

Baicalin treats cerebral ischemia reperfusion-induced brain edema in rats by inhibiting TRPV4 and AQP4 of astrocytes / 中国中药杂志

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.

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.

Active lifestyle enhances protein expression profile in subjects with Lewy body pathology / O estilo de vida ativo melhora o perfil de expressão de proteínas em indivíduos com a patologia de corpos de lewy

ABSTRACT. Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue. Objective: We aimed to evaluate, by immunohistochemistry, astrocytes, tyrosine hydroxylase (TH) and structural proteins expression (neurofilaments and microtubules — MAP2) changes in postmortem brain samples of individuals with Lewy body pathology. Methods: Braak PD stage≥III samples, classified by neuropathology analysis, from The Biobank for Aging Studies were classified into active (n=12) and non-active (n=12) groups, according to physical activity lifestyle, and paired by age, sex and Braak staging. Substantia nigra and basal ganglia were evaluated. Results: Groups were not different in terms of age or gender and had similar PD neuropathological burden (p=1.00). We observed higher TH expression in the active group in the substantia nigra and the basal ganglia (p=0.04). Astrocytes was greater in the non-active subjects in the midbrain (p=0.03) and basal ganglia (p=0.0004). MAP2 levels were higher for non-active participants in the basal ganglia (p=0.003) and similar between groups in the substantia nigra (p=0.46). Neurofilament levels for non-active participants were higher in the substantia nigra (p=0.006) but not in the basal ganglia (p=0.24). Conclusion: Active lifestyle seems to promote positive effects on brain by maintaining dopamine synthesis and structural protein expression in the nigrostriatal system and decrease astrogliosis in subjects with the same PD neuropathology burden.

RESUMO. Estudos dos efeitos da atividade física relataram melhora nos sintomas e na qualidade de vida de pacientes com doença de Parkinson (DP). Além disso, alterações morfológicas do cérebro após o exercício físico foram relatadas em modelos animais da DP. No entanto, essas mudanças relacionadas ao estilo de vida não foram avaliadas em tecido cerebral post-mortem. Objetivo: Avaliar a expressão de astrócitos, tirosina hidroxilase (TH) e a expressão de proteínas estruturais (neurofilamentos e microtúbulos — MAP2) por imuno-histoquímica, em amostras cerebrais post-mortem de indivíduos com corpos de Lewy. Métodos: Amostras com estágio de Braak para DP≥III, classificação neuropatológica, fornecidas pelo biobanco de estudos do envelhecimento foram classificadas em grupos ativos (n=12) e não ativos (n=12), de acordo com o estilo de vida (atividade física), e pareados por idade, sexo e estadiamento de Braak. Analisou-se a substância negra e gânglios da base. Resultados: Idade, sexo e classificação para DP foram semelhantes (p=1,00). Observou-se maior expressão de TH no grupo ativo (p=0,04). Amostras de não ativos revelaram maior expressão de astrócitos no mesencéfalo (p=0,03) e nos gânglios da base (p=0,0004); MAP2 nos gânglios da base (p=0,003); os níveis de neurofilamentos foram maiores na substância negra (p=0,006). Conclusão: O estilo de vida ativo parece promover efeitos positivos no cérebro, mantendo a síntese de dopamina e a expressão estrutural de proteínas no sistema nigrostriatal e com diminuição da ativação de astrócitos em indivíduos com a mesma classificação neuropatológica para a DP.

Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1 / 神经科学通报·英文版

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

Astrocytes in depression and Alzheimer's disease / 医学前沿

Astrocytes are an abundant subgroup of cells in the central nervous system (CNS) that play a critical role in controlling neuronal circuits involved in emotion, learning, and memory. In clinical cases, multiple chronic brain diseases may cause psychosocial and cognitive impairment, such as depression and Alzheimer's disease (AD). For years, complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability, resulting in gradual loss of self-care ability, lower life qualities, and vast burden on human society. Interestingly, correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological disease. As a kind of multifunctional glial cell in the CNS, astrocytes maintain physiological function via supporting neuronal cells, modulating pathologic niche, and regulating energy metabolism. Mounting evidence has shown that astrocytic dysfunction is involved in the progression of depression and AD. We herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD, with an implication of potential therapeutic avenue for these diseases by targeting astrocytes.

Elemene Emulsion Injection Administration Reduces Neuropathic Pain by Inhibiting Astrocytic NDRG2 Expression within Spinal Dorsal Horn / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanisms underlying elemene-induced analgesia in rats with spared nerve injury (SNI).@*METHODS@#Sixty-five rats were equally divided into 5 groups using a random number table: naive group, sham group, SNI group, SNI + elemene (40 mg·kg@*RESULTS@#The SNI rat model exhibited a significant decrease in paw withdrawal threshold and exploratory behaviour in the EPM (P<0.05). Consecutive administration of elemene alleviated SNI-induced mechanical allodynia and anxiety in rats (P<0.05). Immunohistochemical data showed that elemene decreased SNI-induced upregulation of NDRG2 within the SDH (P<0.05). Double immunofluorescent staining data further showed that elemene decreased SNI-induced upregulation of the number of GFAP immunoreactive (-ir), NDRG-ir, and GFAP/NDRG2 double-labelled cells within the SDH (P<0.05). Immunoblotting data showed that elemene decreased SNI-induced upregulation of GFAP and NDRG2 within the SDH (P<0.05).@*CONCLUSION@#Elemene possibly alleviated neuropathic pain by downregulating the expression of NDRG2 in spinal astrocytes in a rat model of SNI.

Advance in mechanisms of glial scarring after stroke and intervention of traditional Chinese medicine / 中国中药杂志

When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.

Biological characteristics and functions of NG2-glia / 生理学报

NG2-glia are a major type of glial cells that are widely distributed in the central nervous system (CNS). Under physiological conditions, they mainly differentiate into oligodendrocytes and contribute to the myelination of axons, so they are generally called oligodendrocyte progenitor cells. Emerging evidence suggests that NG2-glia not only act as the precursors of oligodendrocytes but also possess many other biological properties and functions. For example, NG2-glia can form synapse with neurons and participate in energy metabolism and immune regulation. Under pathological conditions, NG2-glia can also differentiate into astrocytes, Schwann cells and even neurons, which are involved in CNS injury and repair. Therefore, a deeper understanding of the biological characteristics and functions of NG2-glia under physiological and pathological conditions will be helpful for the treatment of CNS injury and disease. This article reviews the recent advances in the biological characteristics and functions of NG2-glia.

Nuclear Factor-κB Signaling Mediates Antimony-induced Astrocyte Activation / 生物医学与环境科学（英文）

Objective@#Antimony (Sb) has recently been identified as a novel nerve poison, although the cellular and molecular mechanisms underlying its neurotoxicity remain unclear. This study aimed to assess the effects of the nuclear factor kappa B (NF-κB) signaling pathway on antimony-induced astrocyte activation.@*Methods@#Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of p65. The expression of protein in brain tissue sections was detected by immunohistochemistry. The levels of mRNAs were detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR).@*Results@#Antimony exposure triggered astrocyte proliferation and increased the expression of two critical protein markers of reactive astrogliosis, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP), indicating that antimony induced astrocyte activation @*Conclusion@#Antimony activated astrocytes by activating the NF-κB signaling pathway.

Absence of BAX differentially affects astrocyte density in the mouse cortex and hippocampus / 生理学报

Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.

Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.

Relación entre el coeficiente de difusión aparente y la celularidad de gliomas en centro de tercer nivel de Panamá / Relationship between the apparent diffusion coefficient and cellularity of gliomas in tertiary care center of Panamá

Introducción: Los gliomas son tumores malignos altamente celulares del sistema ner­ vioso central. Su grado histológico preoperatorio es de utilidad en el manejo quirúrgico, por lo que la resonancia magnética con secuencias avanzadas intenta brindar mayor información tumoral. Objetivo: Relacionar el coeficiente aparente de difusión (CAD) y celularidad de los gliomas de pacientes entre enero 2015 a diciembre 2017. Metodo­ logía: Retrospectivamente se obtuvieron de archivos clínicos la edad, sexo, tipo, grado histológico y sitio anatómico. Se calculó el CAD en 5mm 2 en los estudios de resonancia magnética preoperatorias y se utilizó las laminillas para conteo de celularidad en 5mm 2 digitalmente. Se utilizó análisis estadísticos descriptivos y coeficiente de correlación entre CDA con celularidad. Se utilizaron valores de p < 0.05 para significancia estadís­ tica. Resultados: 46 casos fueron incluidos, 56.5% fueron hombres. El rango de 41­64 años fueron los más afectados. El glioblastoma fue el tipo histológico más frecuente (47.8%), así como los gliomas de alto grado (73.9%). El 95.7% fueron supratentoriales. La celularidad promedio fue de 3970 ± 2900 vs 2436 ± 948 núcleos/5mm 2 (p = 0.13), con valores promedio de CDA mínimo de 0.813 x 10­3 ± 0.229 mm 2 /s vs 1.052 x 10­3 ± 0.196 mm 2 /s (p = 0.002), para los gliomas de alto y bajo grado respectivamente. La co­ rrelación entre CDA y celularidad fue débil (R = ­ 0.13, p = 0.37). Conclusión: Existe co­ rrelación débil inversamente proporcional entre el CDA y la celularidad con distinción de gliomas de bajo y alto grado con valores de CDA mínimos

Introduction: Gliomas are highly cellular malignant tumors of the central nervous sys­ tem. Its preoperative histological grade is useful in surgical management, so magnetic resonance imaging with advanced sequences tries to provide more tumor information. Objective: Correlate apparent diffusion coefficient (ADC) and cellularity of gliomas of patients between January 2015 to December 2017. Methodology: Data of age, sex, ty­ pe, histologic grade and anatomic site were retrospectively obtained from clinical archi­ ves. The preoperative magnetic resonance ADC was calculated in a 5 mm 2 region of interest and the microscope slides were used for the cellularity digitally count in 5 mm 2 . Descriptive statistical analysis and correlation coefficient between ADC and cellularity were used. Values of p <0.05 were used for statistical significance. Results: 46 cases were included, 56.5% were men. The 41­64 years ranges were the most affected. Glio­ blastoma was the most frequent histological type (47.8%), as well as high grade glio­ mas (73.9%). 95.7% were supratentorial. The average cellularity was 3970 ± 2900 vs 2436 ± 948 nuclei/ 5mm 2 (p = 0.13), with average minimum ADC values of 0.813 x 10­3 ± 0.229 mm 2 /s vs 1052 x 10­3 ± 0.196 mm 2 /s (p = 0.002), for high­ and low­grade glio­ mas, respectively. The correlation between ADC and cellularity was weak (R = ­ 0.13, p = 0.37). Conclusions: There is a weak inversely proportional correlation between ADC and cellularity. With distinction of low­ and high­grade gliomas with minimum ADC values

Early and late neuropathological features of meningoencephalitis associated with Maraba virus infection

Maraba virus is a member of the genus Vesiculovirus of the Rhabdoviridae family that was isolated in 1983 from sandflies captured in the municipality of Maraba, state of Pará, Amazônia, Brazil. Despite 30 years having passed since its isolation, little is known about the neuropathology induced by the Maraba virus. Accordingly, in this study the histopathological features, inflammatory glial changes, cytokine concentrations, and nitric oxide activity in the encephalon of adult mice subjected to Maraba virus nostril infection were evaluated. The results showed that 6 days after intranasal inoculation, severe neuropathological-associated disease signs appeared, including edema, necrosis and pyknosis of neurons, generalized congestion of encephalic vessels, and intra- and perivascular meningeal lymphocytic infiltrates in several brain regions. Immunolabeling of viral antigens was observed in almost all central nervous system (CNS) areas and this was associated with intense microglial activation and astrogliosis. Compared to control animals, infected mice showed significant increases in interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (INF)-γ, MCP-1, nitric oxide, and encephalic cytokine levels. We suggest that an exacerbated inflammatory response in several regions of the CNS of adult BALB/c mice might be responsible for their deaths.

The effect of rosmarinic acid on deformities occurring in brain tissue by craniectomy method. Histopathological evaluation of IBA-1 and GFAP expressions

Abstract Purpose To investigate the role of Rosmarinic acid (RA) in the prevention of traumatic brain injury and the immunohistochemical analysis of IBA-1 and GFAP expressions. Methods Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows; control group, traumatic brain injury (TBI) group, and TBI+RA group. After traumatic brain injury, blood samples were taken from the animals and analyzed with various biochemical markers. And then IBA-1 and GFAP expressions were evaluated immunohistochemically. Results Significant results were obtained in all biochemical parameters between groups. Immunohistochemical sections showed IBA-1 not only in microglia and macrophage activity but also in degenerative neurons in blood vessel endothelial cells. However, GFAP reaction and post-traumatic rosmarinic acid administration showed positive expression in astrocytes with regular structure around the blood vessel. Conclusion Rosmarinic acid in blood vessel endothelial cells showed that preserving the integrity of astrocytic structure in the blood brain barrier may be an important antioxidant.

Estudio anatómico del hipocampo como una de las regiones de neurogénesis más relevante / Anatomical study of the hippocampus as one of the most relevant neurogenesis regions

Los avances tecnológicos en el campo de la medicina regenerativa han abierto un sin fin de posibilidades terapéuticas, que hace algún tiempo hubiera sido imposible de concebir. Dichos avances se han enfocado en el estudio regenerativo de células propias del Sistema Nervioso Central (SNC), gracias a la identificación plena de las funciones de las Células Madre Neurales (CMNs) y de ciertos marcadores neurogliales que intervienen en la formación de células troncales neuronales, originando no solo astrocitos, sino también neuronas, oligodendrocitos y células ependimarias. Teniendo en cuenta estos aspectos, la presente revisión bibliográfica se centra en el estudio anatómico de la zona del hipocampo como una de las regiones génicas más importantes e interesantes. Su papel fundamental es la formación de nichos neurogénicos, lugar donde se producen los procesos de diferenciación y formación de nuevas neuronas a partir de células troncales presentes durante toda la vida.

Technological advances in the field of regenerative medicine have opened an endless of therapeutic possibilities, that some time ago would have been impossible even to conceive. These developments have focused their attention so important in the study of regenerative cells of the Central Nervous System (CNS), thanks to the full identification of the functions of neural stem cells (NSCs) and some of the glial markers involved in the formation of neural stem cells, causing not only astrocytes, but also neurons, oligodendrocytes, and ependymal cells. Having this in mind, the present review focuses its attention on the anatomical study of the area of the hippocampus as one of the most important and interesting gene regions, from its fundamental role in the formation of neurogenic niches, place where the processes of differentiation and formation of new neurons from neural stem cells present throughout life.

Characteristics of electrophysiological changes in the process of astrocytes pyroptosis after hyperoxia exposure / 中南大学学报(医学版)

OBJECTIVES@#To observe the electrophysiological changes of astrocytes in the process of hyperoxia induced apoptosis and analyze the relationship between electrophysiological characteristics and morphological changes.@*METHODS@#Astrocytes were exposed to 90% hyperoxia for 12-72 h. The electrophysiological characteristics of astrocytes in each group were detected by patch clamp technique, and the morphological characteristics of astrocytes were observed at the same time. Then the same batch of astrocytes were collected, and the expression levels of caspase-1, caspase-3, gasdermin D (GSDMD) and gasdermin E (GSDME) were detected by Western blotting.@*RESULTS@#From 12 h to 72 h after hyperoxia exposure, the inward current was significantly lower than that of the control group (0.05). At each time point, the morphology of cells changed correspondingly. Western blotting showed that the expression of caspase-1 was increased significantly at 24 h and decreased significantly at 72 h after hyperoxia exposure (0.05), but began to decrease at 48 h (<0.05); GSDME increased gradually at 24 h after hyperoxia exposure (<0.05).@*CONCLUSIONS@#Under hyperoxia exposure, the ion channels of astrocytes are damaged, which can maintain the dysfunction of ion homeostasis, activate GSDME, induce the damaged cells to break away from the apoptotic pathway, and mediate the pyroptosis.