Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling / 中国结合医学杂志

OBJECTIVE@#To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).@*METHODS@#According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.@*RESULTS@#EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.@*CONCLUSION@#EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

Glia Connect Inflammation and Neurodegeneration in Multiple Sclerosis / 神经科学通报·英文版

Multiple sclerosis (MS) is regarded as a chronic inflammatory disease that leads to demyelination and eventually to neurodegeneration. Activation of innate immune cells and other inflammatory cells in the brain and spinal cord of people with MS has been well described. However, with the innovation of technology in glial cell research, we have a deep understanding of the mechanisms of glial cells connecting inflammation and neurodegeneration in MS. In this review, we focus on the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the pathogenesis of MS. We mainly focus on the connection between glial cells and immune cells in the process of axonal damage and demyelinating neuron loss.

The Structure and Function of Glial Networks: Beyond the Neuronal Connections / 神经科学通报·英文版

Glial cells, consisting of astrocytes, oligodendrocyte lineage cells, and microglia, account for >50% of the total number of cells in the mammalian brain. They play key roles in the modulation of various brain activities under physiological and pathological conditions. Although the typical morphological features and characteristic functions of these cells are well described, the organization of interconnections of the different glial cell populations and their impact on the healthy and diseased brain is not completely understood. Understanding these processes remains a profound challenge. Accumulating evidence suggests that glial cells can form highly complex interconnections with each other. The astroglial network has been well described. Oligodendrocytes and microglia may also contribute to the formation of glial networks under various circumstances. In this review, we discuss the structure and function of glial networks and their pathological relevance to central nervous system diseases. We also highlight opportunities for future research on the glial connectome.

Roles of NG2 Glia in Cerebral Small Vessel Disease / 神经科学通报·英文版

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms / 神经科学通报·英文版

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.

Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders / 神经科学通报·英文版

The concept of the glial-vascular unit (GVU) was raised recently to emphasize the close associations between brain cells and cerebral vessels, and their coordinated reactions to diverse neurological insults from a "glio-centric" view. GVU is a multicellular structure composed of glial cells, perivascular cells, and perivascular space. Each component is closely linked, collectively forming the GVU. The central roles of glial and perivascular cells and their multi-level interconnections in the GVU under normal conditions and in central nervous system (CNS) disorders have not been elucidated in detail. Here, we comprehensively review the intensive interactions between glial cells and perivascular cells in the niche of perivascular space, which take part in the modulation of cerebral blood flow and angiogenesis, formation of the blood-brain barrier, and clearance of neurotoxic wastes. Next, we discuss dysfunctions of the GVU in various neurological diseases, including ischemic stroke, spinal cord injury, Alzheimer's disease, and major depression disorder. In addition, we highlight the possible therapies targeting the GVU, which may have potential clinical applications.

The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities / 神经科学通报·英文版

Glioma is the most common and lethal intrinsic primary tumor of the brain. Its controversial origins may contribute to its heterogeneity, creating challenges and difficulties in the development of therapies. Among the components constituting tumors, glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation. Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor, in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation. Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states, glial, neural, and immune cell populations in the tumor microenvironment. Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy. Here, we discuss the heterogeneity and relevant functions of tumor cell state, microglia, monocyte-derived macrophages, and neurons in glioma, highlighting their bilateral effects on tumors. Finally, we describe potential therapeutic approaches and targets beyond standard treatments.

Immunological Markers for Central Nervous System Glia / 神经科学通报·英文版

Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.

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.

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.

Biomarcadores gliais da doença de Alzheimer / Glial biomarkers of Alzheimer's disease

Introdução: A neuroinflamação associada às células gliais é um elemento importante do processo patológico da doença de Alzheimer (DA). Este estudo apresenta uma revisão dos marcadores gliais quitinase 3-like 1 (YKL-40), do receptor desencadeado expresso nas células mieloides 2 (Triggering receptor expressed on myeloid cells 2 ­ TREM2), da proteína acídica fibrilar glial (GFAP) e da proteína B S100 ligante de cálcio (S100B). Métodos: Nesta revisão são analisados os marcadores gliais YKL-40, TREM2, GFAP e S100B presentes em sangue e/ou líquido cefalorraquidiano (LCR), a partir de estudos publicados até 2020 nos bancos de dados do PubMed, Medline e Periódicos Capes. Resultados: Foram recuperados 233 documentos, dentre os quais foram incluídos 60. Todos os marcadores se encontram aumentados na DA em LCR ­ YKL-40 e TREM2 solúvel (sTREM2), já na fase pré-clínica ­, e em sangue, e estão correlacionados ao declínio cognitivo. No entanto, nenhum dos marcadores analisados apresentou grande potencial para o diagnóstico diferencial. Além da proteína TREM2 solúvel no LCR, no sangue também se pode identificar alteração nos níveis do RNAm de TREM2. GFAP sanguíneo mostra ser o melhor em distinguir controles de pacientes com Alzheimer. Há evidências de um efeito protetivo da ativação glial em reação ao acúmulo amiloide. Conclusão: Os marcadores gliais no geral têm pouca utilidade para o diagnóstico diferencial, mas podem auxiliar no prognóstico e como biomarcadores inespecíficos para doenças neurodegenerativas. (AU)

Introduction: Glial cell-associated neuroinflammation is a driving force for the pathological process of Alzheimer's disease (AD). This study is a systematic review aimed to analyze the following glial markers: chitinase-3-like protein 1 (YKL-40), triggering receptor expressed on myeloid cells 2 (TREM2), glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B). Methods: The PubMed, MEDLINE and CAPES Journals databases were searched for studies published until 2020 that addressed blood and/or cerebrospinal fluid (CSF) levels of YKL-40, TREM2, GFAP and S100B. Results: A total of 233 articles were retrieved, of which 60 were included in this study. All CSF ­ YKL-40 and soluble TREM2 (sTREM2) in preclinical stage ­ and blood biomarker levels were elevated for AD and were correlated to cognitive decline. None of the analyzed biomarkers showed promising results for differential diagnosis. Besides CSF sTREM2 levels, blood TREM2 mRNA levels were also altered in AD. Blood GFAP levels seem to be the best option for distinguishing controls from AD patients.' There is evidence of a protective role of glial activation in amyloid accumulation. Conclusion: Glial markers in general are of little use for differential diagnosis but can assist in prognosis and as nonspecific biomarkers of neurodegenerative diseases. (AU)

Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise / 神经科学通报·英文版

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.

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.

Research progress on transient receptor potential melastatin 2 channel in nervous system diseases / 浙江大学学报·医学版

Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer's disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.

Effects of different materials for partial sciatic nerve ligation on glial cell activation in rat models of chronic constriction injury / 南方医科大学学报

OBJECTIVE@#To compare the effects of different materials for partial sciatic nerve ligation on glial cell activation in the spinal cord in a rat model of chronic constriction injury (CCI).@*METHODS@#SD rats were randomly divided into the sham group (=15), silk suture CCI group (=15) and chromic catgut CCI group (=14). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of the rats were detected at 3, 7, 11 and 15 days after the operation. The changes in the sciatic nerve, the activation of spinal cord glial cells and the expression of inflammatory factors were observed using Western blotting and RT-PCR.@*RESULTS@#At 3 to 15 days after the surgery, MWT and TWL of the rats were significantly lower in silk suture group and chromic catgut group than in the control group ( < 0.05), and was significantly lower in chromic catgut group than in the silk suture group ( < 0.05) at 3 days after the surgery. The results of sciatic nerve myelin staining showed that the sciatic nerve was damaged and demyelinated in both the ligation groups. The expressions of CD11b, GFAP, IL-1β and TNF-α in the two ligation groups were similar and all significantly higher than those in the control group ( < 0.05). IL-6 mRNA level was significantly higher in chromic catgut group than in the silk suture group ( < 0.05).@*CONCLUSIONS@#The CCI models established by partial sciatic nerve ligation with silk suture and chromic catgut all show glial activation, and the inflammatory response is stronger in chromic catgut group.

Envolvimento das células da glia na ação antinociceptiva da toxina phα1ß e da ω-conotoxina mviia na dor inflamatória periférica / Involvement of glial cells in the antinociceptive action of phα1ß toxin and ω-conotoxin mviia in peripheral inflammatory pain

A lesão inflamatória de origem periférica aumenta a sensibilidade sensória a um estímulo mecânico de leve intensidade, provocando dor, um processo conhecido como alodinia. A recente descoberta de que astrócitos e micróglia da medula espinal tornam-se reativos devido à inflamação periférica, sugere que a glia deve estar envolvida na manifestação patológica da dor. Nesta tese, observou-se que a inflamação periférica, induzida pela injeção intraplantar do adjuvante completo de Freund (CFA), causa alodinia mecânica assim como mudanças na glia. Dentre essas mudanças destacamos o aumento de marcadores específicos da glia, aumento da proliferação de astrócitos assim como alterações morfológicas na micróglia, todas elas características do fenótipo reativo da glia. Além disso, este estudo descobriu que a injeção intratecal da toxina de aranha Phα1ß, um peptídeo com ação analgésica que bloqueia canais de cálcio dependente de voltagem (VGCC), reverte todas as alterações da glia da medula espinal causadas pela inflamação periférica. Essas observações, em resumo, sugerem que a toxina Phα1ß, além de sua já reconhecida ação analgésica, também possui efeitos anti-inflamatórios sobre a plasticidade glial.

A peripheral inflammatory injury increases the mechanical sensitivity in response to light-touch, also named as allodynia. The discovery that spinal astrocytes and microglia become reactive to the peripheral inflammation suggests that the glia presumably engage with the pain pathophysiology. Here, we found that the peripheral inflammation induced by intraplantar injection of complete Freund's adjuvant (CFA) produce mechanical allodynia and robust changes in the spinal glial. Among these changes we found an increase of specific glial markers, increment of astrocytes proliferation, elevation of microglia density and morphologic changes, all of them compatible with the glia reactive phenotype. Moreover, we found that intrathecal injection with the analgesic Phα1ß spider toxin, a voltage-gated calcium channel (VGCC) blocker, reverses all the glial pathological features of the peripheral inflammation. We therefore suggest that the Phα1ß toxin, apart from its notable analgesic effects, is also a potent anti-inflammatory compound acting on glial plasticity.

Regulation of Neural Stem Cell Fate by Natural Products

Neural stem cells (NSCs) can proliferate and differentiate into multiple cell types that constitute the nervous system. NSCs can be derived from developing fetuses, embryonic stem cells, or induced pluripotent stem cells. NSCs provide a good platform to screen drugs for neurodegenerative diseases and also have potential applications in regenerative medicine. Natural products have long been used as compounds to develop new drugs. In this review, natural products that control NSC fate and induce their differentiation into neurons or glia are discussed. These phytochemicals enable promising advances to be made in the treatment of neurodegenerative diseases.

Persistent Malfunction of Glymphatic and Meningeal Lymphatic Drainage in a Mouse Model of Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event that often is followed by permanent brain impairments. It is necessary to explore the pathogenesis of secondary pathological damages in order to find effective interventions for improving the prognosis of SAH. Blockage of brain lymphatic drainage has been shown to worsen cerebral ischemia and edema after acute SAH. However, whether or not there is persistent dysfunction of cerebral lymphatic drainage following SAH remains unclear. In this study, autologous blood was injected into the cisterna magna of mice to establish SAH model. One week after surgery, SAH mice showed decreases in fluorescent tracer drainage to the deep cervical lymph nodes (dcLNs) and influx into the brain parenchyma after injection into the cisterna magna. Moreover, SAH impaired polarization of astrocyte aquaporin-4 (AQP4) that is a functional marker of glymphatic clearance and resulted in accumulations of Tau proteins as well as CD3⁺, CD4⁺, and CD8⁺ cells in the brain. In addition, pathological changes, including microvascular spasm, activation of glial cells, neuroinflammation, and neuronal apoptosis were observed in the hippocampus of SAH mice. Present results demonstrate persistent malfunction of glymphatic and meningeal lymphatic drainage and related neuropathological damages after SAH. Targeting improvement of brain lymphatic clearance potentially serves as a new strategy for the treatment of SAH.