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Vascular-Perfusable Human 3D Brain-on-Chip.

UNLABELLED: Development and delivery of treatments for neurological diseases are limited by the tight and selective human blood-brain barrie … y and disease. Here we developed a 3D Brain-Chip system incorporating endothelial cells, pericytes, astrocytes, neurons, microglia, and oligodendroglia from iPSCs. To enable this multicellular 3D co-culture in-chip, we designed a GelChip microfluidic platform using a 3D printing-based approach and dextran-based engineered hydrogel. Leveraging this platform, …

Spatiotemporal Immune Dynamics in Experimental Retinal Ganglion Cell Injury Models.

BACKGROUND: The damage and regeneration of retinal ganglion cells (RGCs) have been extensively studied. Among them, immune cells in differen … isual input pathway displays a distinct immune cell composition, including Müller cells, microglia, astrocytes, T cells, and oligodendrocytes, all of which work together to maintain homeostasis and respond to injury. Some immune cells are specific to certain regions, while others are shared across areas. Furthermore, even within a single glial cell type, the …

The Impacts of FLASH Radiation Therapy and Conventional Radiation Therapy on the Cognitive Abilities of Mice.

PURPOSE: Preclinical studies have demonstrated that FLASH radiation therapy (RT) delivered at ultrahigh-dose rates exerts a preferential nor … FLASH-RT. Two months after irradiation, we assessed the mice's cognitive function and the number of astrocytes and neurons in the hippocampus, then conducted proteomic analyses of their hippocampus. RESULTS: Following the administration of a 20 Gy FLASH-RT dose, the incidence of radiodermatitis was markedly lower than that observed with CONV-RT, accompanied …

Модулятор течения VRAC 1 Потенциальная цель в множественных склерозах.

Множественный склероз (MS) — хроническое иммунопосредованное демиелинирующее заболевание ЦНС. Подчёркиваемый успехом таких методов лечения, разрушающих клетки В, как моноклональные anti-CD20 Клетки антител ritoximab, ocrelizumab и atumumumab, B играют центральную роль в иммунопатологии болезни. Однако целевые антигены патогенной реакции B-клеток в MS остаются неясными. Мы комбинировали поликлональную стимуляцию B-клеток периферийных мононуклеарных клеток крови с микроаварией протеомного протеина по всему организму человека для выявления целевых антигенов MS путем сопоставления образцов из 20 б

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the CNS. Highlighted by the success … LC1 were observed in the CSF of patients with neuroinflammatory diseases other than MS. Neurons and astrocytes were identified as the main cell types expressing MLC1 in the brain of a patient with MS. Injection of anti-MLC1 antibodies into mice with EAE led to strong in vivo binding to cerebral cortical neurons and to the death of 4 of the 7 injected mice. …

Расширенный полиглутамин в ATAXIN1 приводит к потере функции, которая усугубляет остроту множественного склероза в модели мыши EAE.

Ataxin-1 (ATXN1) — белок, в котором расширение его полиглутаминового тракта вызывает нервно-дегенеративное расстройство спинномозговой системы 1 (SCA1) в результате повышения функциональности. Недавно было продемонстрировано, что АТXN1 дикая порода играет защитную роль в регулировании жесткости экспериментального аутоиммунного энцефаломиелита (EAE) — хорошо зарекомендовавшей себя модели мыши для мультиклероза (MS). В этом исследовании дополнительно изучается роль ATXN1 с расширенным полиглутаминым трактом в контексте MS с использованием модели мыши EAE.МЕТОДЫ: Гемизиговые атксны1 (Atxn1 2Q/-)

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVES: Ataxin-1 (ATXN1) is a protein in which expansion of its polyglutamine tract causes the neurodegenerative disorder … on, and greater clinical disability in affected mice. Importantly, the data reveals that neurotoxic astrocytes are activated at acute stage of disease (PID-14) and at the chronic stage of disease (PID-30) neurotoxic astrocytes no longer show signs of activation. The data also demonstrated enhanced infiltration of immune cells into the lesions of mutant mice. …

Dexmedetomidine Attenuated Neuron Death, Cognitive Decline, and Anxiety-Like Behavior by Inhibiting CXCL2 in CA1 Region of AD Mice.

PURPOSE: β-amyloid overload-induced neuroinflammation and neuronal loss are key pathological changes that occur during the progression of Al … immunofluorescence experiments were conducted to evaluate the status of the hippocampal neurons and astrocytes. qRT-PCR was performed to detect the expression of CXCL2, IL-1β, INOS, SPHK1, Bcl2, IFN-γ, and Caspase 1. The malondialdehyde (MDA) level was detected using an ELISA kit. Terminal TUNEL and Fluoro-Jade C (FJC) staining were used to measure the cell …

The Absence of CXCL10 Activity Does Not Affect the Capability of CD8+ T Cells to Migrate and Eliminate the Tissue Cysts of Toxoplasma gondii from the Brains of Chronically Infected Mice.

Toxoplasma gondii forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays key roles in T cell-mediated control of the proliferation of tachyzoites (the acute stage form) of T. gondii during the acute stage of infection, we examined whether CXCL10 is involved in recruiting anti-cyst CD8+ cytotoxic T cells to eliminate the cysts in their brains. We employed adoptive transfer of CD8+ immune T c…

Distinct expression profile reveals glia involvement in the trigeminal system attributing to post-traumatic headache.

BACKGROUND: Post-traumatic headache (PTH) is a common comorbid symptom affecting at least one-third of patients with mild traumatic brain in … thogenesis of PTH. In situ assays also revealed that gliosis of satellite glial cells in the TG and astrocytes in the Sp5C were prominent days after injury. Furthermore, immunohistochemical study revealed a close interaction between activated microglia and reactive astrocytes correlating with increased calretinin interneurons in the Sp5C. CONCLUSIONS: Trans …

OTUD1 ameliorates cerebral ischemic injury through inhibiting inflammation by disrupting K63-linked deubiquitination of RIP2.

BACKGROUND: Inflammatory response triggered by innate immunity plays a pivotal element in the progress of ischemic stroke. Receptor-interact … mice, oxygen glucose deprivation and reoxygenation (OGD/R) models in BV2 cells and primary cultured astrocytes were performed for monitoring of experimental stroke. GSK2983559 (GSK559), a RIP2 inhibitor was intraventricularly administered 30 min before MCAO. Mice brain tissues were collected for TTC staining and histopathology. Protein expression of RIP2, OT …

Enhanced L-β-Aminoisobutyric Acid Is Involved in the Pathophysiology of Effectiveness for Treatment-Resistant Schizophrenia and Adverse Reactions of Clozapine.

Clozapine is an effective antipsychotic for the treatment of antipsychotic-resistant schizophrenia; however, specific types of A/B adverse e … ion, including GABAB-R and the group-III metabotropic glutamate receptor (III-mGluR) using cultured astrocytes, as well as on the thalamocortical hyper-glutamatergic transmission induced by impaired glutamate/NMDA receptors using microdialysis. Clozapine increased astroglial L-BAIBA synthesis in time/concentration-dependent manners. Increased L-BAIBA synthes …

Beneficial effects of the phytoestrogen genistein on hippocampal impairments of spontaneously hypertensive rats (SHR).

Hippocampal neuropathology is a recognized feature of the spontaneously hypertensive rat (SHR). The hippocampal alterations associate with c … We analyzed the expression of doublecortin+ neuronal progenitors, glial fibrillary acidic protein+ astrocytes and ionized calcium-binding adapter molecule 1+ microglia in the CA1 region and dentate gyrus of the hippocampus using immunocytochemistry, whereas a quantitative real-time polymerase chain reaction was used to measure the expression of pro- and ant …

Friends and Foes in Alzheimer's Disease.

Alzheimer's disease (AD) is a disabling neurodegenerative disease. The prognosis is poor, and currently there are no proven effective therapies. Most likely, the etiology is related to cerebral inflammatory processes that cause neuronal damage, resulting in dysfunction and apoptosis of nerve cells. Pathogens that evoke a neuroinflammatory response, collectively activate astrocytes and microglia, which contributes to the secretion of pro-inflammatory cytokines. This leads to the deposit of clustered fragments of beta-amyloid and misfolded tau proteins which do not elicit an adequate immune reac…

P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice.

BACKGROUND: Neuronal accumulation of misfolded microtubule-associated protein tau is a hallmark of neuropathology in Alzheimer's disease, fr … ochemical assessment. GSK1482160 was also tested for exosome secretion from primary cultured murine astrocytes, neurons and microglia in vitro. RESULTS: Oral administration of GSK1482160 significantly reduced accumulation of MC1+ and Alz50+ misfolded tau in hippocampal regions, which was accompanied with reduced accumulation of Tsg101, an exosome marker, in …

Gene replacement ameliorates deficits in mouse and human models of cyclin-dependent kinase-like 5 disorder.

Cyclin-dependent kinase-like 5 disorder is a severe neurodevelopmental disorder caused by mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene. It predominantly affects females who typically present with severe early epileptic encephalopathy, global developmental delay, motor dysfunction, autistic features and sleep disturbances. To develop a gene replacement therapy, we initially characterized the human CDKL5 transcript isoforms expressed in the brain, neuroblastoma cell lines, primary astrocytes and embryonic stem cell-derived cortical interneurons. We found that the isoform…

Carvone protects against paclitaxel-induced retinal and optic nerve cytotoxicity: a histopathological study.

Purpose: Carvone (CVN) is a natural monoterpene found in essential oils of many aromatic plant species. In this study, we investigated the p … normal. In PTX group all eyes (6/6) demonstrated severe vacuolization and decrease in the number of astrocytes and oligodendrocytes, while 3 eyes (3/6) demonstrated marked single cell necrosis. In PTX-CVN group, 4 eyes (4/6) demonstrated moderate vacuolization while, 2 eyes (2/6) had none. Compared with PTX group, 1 eye (1/6) in PTX-CVN group demonstrated a …

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer.

The active vitamin D hormone, 1,25-dihydroxyvitamin D3 , exerts many physiological actions in the body, including effects on the nervous system. Studies of steroidogenesis in cells of the nervous system and elsewhere not only indicate that 1,25-dihydroxyvitamin D3 affects steroidogenic pathways but also suggest varying responses in different cell types. For example, 1,25-dihydroxyvitamin D3 stimulates the expression of aromatase in human glioma but not in human neuroblastoma cells or rat astrocytes. However, in astrocytes, 1,25-dihydroxyvitamin D3 suppresses 3β-hydroxysteroid dehydrogenase and…

Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation.

Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lo … ained from 11 human cadavers for histological analyses. Neuronal bodies and glial cells (microglia, astrocytes and oligodendrocytes) were immunostained, microphotographed and counted using image analysis software. Statistical analyses were carried out to establish significant differences of neuronal and glial populations among the selected segments, between …

The impact of substance abuse on HIV-mediated neuropathogenesis in the current ART era.

Approximately 37 million people worldwide are infected with human immunodeficiency virus (HIV). One highly significant complication of HIV infection is the development of HIV-associated neurocognitive disorders (HAND) in 15-55% of people living with HIV (PLWH), that persists even in the antiretroviral therapy (ART) era. The entry of HIV into the central nervous system (CNS) occurs within 4-8 days after peripheral infection. This establishes viral reservoirs that may persist even in the presence of ART. Once in the CNS, HIV infects resident macrophages, microglia, and at low levels, astrocytes.…

Yi-nao-jie-yu Prescription Exerts a Positive Effect on Neurogenesis by Regulating Notch Signals in the Hippocampus of Post-stroke Depression Rats.

Post-stroke depression (PSD) is one of the most frequent complications of stroke. The Yi-nao-jie-yu prescription (YNJYP) is an herbal prescr … rons of newly born cells in the hippocampal dentate gyrus, and increased the differentiation toward astrocytes, effects that were reversed by YNJYP, particularly at 4 weeks. At 2 weeks, compared with the stroke group, expression of target gene Hes5 mRNA transcripts in the PSD group decreased, but increased after treatment with YNJYP. At 4 weeks, compared wit …

Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury.

BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP-2) regulates the bioavailability, transportation, and localization of insuli … we show that ischemia causes changes in the distribution of IGFBP-2 in primary cortical neurons and astrocytes. In addition, we show using the transient middle cerebral artery occlusion (MCAO) model in mice that there is a significant increase in IGFBP-2 levels in the stroke penumbra and core after 72 h. This correlated with an overall increase in IGF-I afte …