Neurochemical Research, Journal Year: 2021, Volume and Issue: 47(3), P. 517 - 530
Published: Oct. 20, 2021
Language: Английский
Neuron, Journal Year: 2022, Volume and Issue: 111(2), P. 190 - 201.e8
Published: Nov. 16, 2022
Oligodendrocyte precursor cells (OPCs) undergo an extensive and coordinated migration in the developing CNS, using pre-formed scaffold of developed blood vessels as their physical substrate for migration. While OPC association with vasculature is critical dispersal, equally important permitting differentiation proper myelination target axons appropriate timely detachment, but regulation this process remains unclear. Here we demonstrate a correlation between developmental formation astrocytic endfeet on termination perivascular Ex vivo live imaging shows that astrocyte physically displace OPCs from vasculature, genetic abrogation endfoot hinders both detachment subsequent differentiation. Astrocyte-derived semaphorins 3a 6a act to repel at cessation and, so doing, permit by insulating them maturation inhibitory endothelial niche.
Language: Английский
Citations
40
Journal of Neuroinflammation, Journal Year: 2020, Volume and Issue: 17(1)
Published: Oct. 13, 2020
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive degeneration and loss neurons in specific regions central nervous system. Chronic activation immune cells resident brain, peripheral cell trafficking across blood-brain barrier, release inflammatory neurotoxic factors, appear critical contributors neuroinflammatory response that drives progression neurodegenerative processes AD. As neuro-immune network impaired course AD, this review aimed to point out essential supportive role innate adaptive either normal brain as well recovery from injury. Since a fine-tuning appears crucial ensure proper system functioning, we focused on TNF superfamily member, TNF-related apoptosis-inducing ligand (TRAIL), which modulates both pathogenesis several immunological disorders and, particular, AD-related neuroinflammation. We here summarized mounting evidence potential involvement TRAIL signaling AD pathogenesis, with aim provide clearer insights about novel therapeutic approaches
Language: Английский
Citations
64
Cells, Journal Year: 2020, Volume and Issue: 9(4), P. 977 - 977
Published: April 15, 2020
Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain (TBI). A better understanding of their role the diagnosis, characterization, and management TBI is essential for upcoming clinical implementation. In current investigation, we aimed to explore longitudinal trajectories patients with moderate-to-severe TBI, evaluate relation free-circulating counterpart patient imaging parameters. Exosomal levels glial (glial fibrillary acidic protein (GFAP)) neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), total-tau (t-tau)) were measured serum 21 up 5 days after using single molecule array (Simoa) technology. Group-based trajectory analysis was used generate distinct temporal profiles. We found altered profiles following injury. The dynamics related markers, although correlated, showed differences. Patients diffuse displayed higher acute NFL GFAP concentrations than those focal lesions. UCH-L1 profile characterized by acutely elevated values a secondary steep rise associated early mortality (n = 2) sensitivity specificity 100%. Serum yielded important diagnostic prognostic information represent novel means unveil underlying pathophysiology TBI. Our findings support utility as potential tools improve phenotyping practice therapeutic trials.
Language: Английский
Citations
56
Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15
Published: June 21, 2021
The pathology in neurodegenerative diseases is often accompanied by inflammation. It well-known that many cells within the central nervous system (CNS) also contribute to ongoing neuroinflammation, which can promote neurodegeneration. Multiple sclerosis (MS) both an inflammatory and disease there a complex interplay between resident CNS mediate myelin axonal damage, this communication network vary depending on subtype chronicity of disease. Oligodendrocytes, myelinating cell CNS, their precursors, oligodendrocyte precursor (OPCs), are thought as targets autoimmune during MS several animal models MS; however, emerging evidence OPCs actively inflammation directly indirectly contributes Here we discuss contributors progression starting with lesion murine amenable studying particular aspects We then review how themselves play active role promoting neuroinflammation neurodegeneration, other including microglia, astrocytes, neurons impact OPC function. Further, outline very pleiotropic role(s) cytokines secreted factors classically described solely deleterious its models, but fact, have neuroprotective functions return homeostasis, part via modulation Finally, since affects patients from onset throughout lifespan, aging function recovery. becoming clear not simply bystander uncovering roles they different stages will help uncover potential new avenues for therapeutic intervention.
Language: Английский
Citations
55
Neuroscience & Biobehavioral Reviews, Journal Year: 2021, Volume and Issue: 124, P. 193 - 215
Published: Feb. 6, 2021
Language: Английский
Citations
43
Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)
Published: Feb. 8, 2022
Tissue damage and cellular destruction are the major events in traumatic brain injury (TBI), which trigger sterile neuroimmune neuroinflammatory responses brain. While appropriate acute transient facilitate repair adaptation of injured tissues, prolonged excessive exacerbate damage. The mechanisms that control intensity duration TBI largely remain elusive.We used controlled cortical impact (CCI) model to study role immune checkpoints (ICPs), key regulators homeostasis, regulation vivo.We found de novo expression PD-L1, a potent inhibitory ICP, was robustly transiently induced reactive astrocytes, but not microglia, neurons, or oligodendrocyte progenitor cells (OPCs). These PD-L1+ astrocytes were highly enriched form dense zone around lesion. Blockade PD-L1 signaling enlarged tissue cavity size, increased infiltration inflammatory Ly-6CHigh monocytes/macrophages (M/Mɸ) tissue-repairing Ly-6CLowF4/80+ M/Mɸ, worsened outcomes mice. gene knockout enhanced production CCL2 is best known for its ability interact with cognate receptor CCR2 on M/Mϕ chemotactically recruit these into sites. Mechanically, likely exhibits dual activities prevention through (1) PD-1/PD-L1 axis suppress activity brain-infiltrating PD-1+ cells, such as T (2) intrinsic regulate timing astrocyte reactions TBI.PD-L1+ act gatekeeper TBI-related responses, thereby opening novel avenue ICP-neuroimmune axes pathophysiology other neurological disorders.
Language: Английский
Citations
37
Glia, Journal Year: 2022, Volume and Issue: 70(8), P. 1554 - 1580
Published: March 17, 2022
Studies over the past two decades have demonstrated that astrocytes are tightly associated with neurons and play pivotal roles in neural circuit development, operation, adaptation health disease. Nevertheless, precisely how integrate diverse neuronal signals, modulate structure function at multiple temporal spatial scales, influence animal behavior or disease through aberrant excitation molecular output remains unclear. This Perspective discusses new state-of-the-art approaches, including fluorescence indicators, opto- chemogenetic actuators, genetic targeting tools, quantitative behavioral assays, computational methods, might help resolve these longstanding questions. It also addresses complicating factors interpreting astrocytes' role regulation behavior, such as their heterogeneity, metabolism, inter-glial communication. Research on questions should provide a deeper mechanistic understanding of astrocyte-neuron assemblies' function, complex behaviors,
Language: Английский
Citations
37
Life, Journal Year: 2022, Volume and Issue: 12(6), P. 910 - 910
Published: June 17, 2022
Stroke is a leading cause of death and long-term disability worldwide. Astrocytes structurally compose tripartite synapses, blood–brain barrier, the neurovascular unit perform multiple functions through cell-to-cell signaling neurons, glial cells, vasculature. The crosstalk astrocytes other cells complicated incompletely understood. Here we review role in response to ischemic stroke, both beneficial detrimental, from cell–cell interaction perspective. Reactive provide neuroprotection antioxidation antiexcitatory effects metabolic support; they also contribute neurorestoration involving neurogenesis, synaptogenesis, angiogenesis, oligodendrogenesis by with stem cell lineage. In meantime, reactive play vital neuroinflammation brain edema. Glial scar formation chronic phase hinders functional recovery. We further discuss astrocyte enriched microRNAs exosomes regulation stroke. addition, latest notion subsets astrocytic activity revealed optogenetics mentioned. This discusses current understanding intimate molecular conversation between outlines its potential implications after “Neurocentric” strategies may not be sufficient for neurological protection recovery; future therapeutic could target astrocytes.
Language: Английский
Citations
37
Cancers, Journal Year: 2022, Volume and Issue: 14(5), P. 1207 - 1207
Published: Feb. 25, 2022
Intercellular communication is essential for tissue homeostasis and function. Understanding how cells interact with each other paramount, as crosstalk between often dysregulated in diseases can contribute to their progression. Cells communicate through several modalities, including paracrine secretion specialized structures ensuring physical contact them. Among these intercellular structures, tunneling nanotubes (TNTs) are now recognized a means of cell-to-cell the exchange cellular cargo, controlled by variety biological triggers, described here. fundamental brain It allows dialogue many cells, neurons, astrocytes, oligodendrocytes, glial microglia, necessary proper development function brain. We highlight here role TNTs connecting physiological functioning pathologies such stroke, neurodegenerative diseases, gliomas. processes could pave way future therapies.
Language: Английский
Citations
35
Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 17(12), P. 2623 - 2623
Published: Jan. 1, 2022
Ras homolog (Rho)-associated kinases (ROCKs) belong to the serine-threonine kinase family, which plays a pivotal role in regulating damage, survival, axon guidance, and regeneration of neurons. ROCKs are also involved biological effects immune cells glial cells, as well development neurodegenerative disorders such Alzheimer's disease, Parkinson's multiple sclerosis. Previous studies by us others confirmed that inhibitors attenuated symptoms progression experimental models abovementioned diseases inhibiting neuroinflammation, imbalance, repairing blood-brain barrier, promoting nerve repair myelin regeneration. Fasudil, first inhibitor be used clinically, has good therapeutic effect on diseases. Fasudil increases activity neural stem mesenchymal thus optimizing cell therapy. This review will systematically describe, for time, abnormal activation T B microglia, astrocytes, oligodendrocytes, pericytes central nervous system, summarize potential fasudil several diseases, clarify possible cellular molecular mechanisms inhibition. proposes is novel treatment, especially combination with cell-based Findings from this add support further investigation its treatment
Language: Английский
Citations
33