Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID

Cells, Год журнала: 2023, Номер 12(5), С. 688 - 688

Опубликована: Фев. 22, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae SARS-CoV-2 (PASC), referred to as “Long-COVID,” characterized by persistent physical mental fatigue. However, exact pathogenetic mechanisms affecting brain are still not well-understood. There is increasing evidence neurovascular inflammation in brain. precise role neuroinflammatory response that contributes severity long COVID pathogenesis clearly understood. Here, we review reports spike protein can cause blood–brain barrier (BBB) dysfunction damage neurons either directly, or via activation mast cells microglia release various molecules. Moreover, provide recent novel flavanol eriodictyol particularly suited for development an effective treatment alone together with oleuropein sulforaphane (ViralProtek®), all which have potent anti-viral anti-inflammatory actions.

Язык: Английский

---

Fully automated sequential immunofluorescence (seqIF) for hyperplex spatial proteomics

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Окт. 9, 2023

Tissues are complex environments where different cell types in constant interaction with each other and non-cellular components. Preserving the spatial context during proteomics analyses of tissue samples has become an important objective for applications, one most being investigation tumor microenvironment. Here, we describe a multiplexed protein biomarker detection method on COMET instrument, coined sequential ImmunoFluorescence (seqIF). The fully automated uses successive applications antibody incubation elution, in-situ imaging enabled by integrated microscope microfluidic chip that provides optimized optical access to sample. We show seqIF data sample such as healthy tissue, including 40-plex single section is obtained less than 24 h, using off-the-shelf antibodies. also present extensive characterization developed method, elution efficiency, epitope stability, repeatability reproducibility, signal uniformity, dynamic range, addition marker panel optimization strategies. streamlined workflow antibodies, quality enabling downstream analysis, ease reaching hyperplex levels make suitable immune-oncology research disciplines requiring paving way its adoption clinical settings.

Язык: Английский

---

Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood–Brain Barrier

Cells, Год журнала: 2024, Номер 13(2), С. 150 - 150

Опубликована: Янв. 12, 2024

The blood-brain barrier (BBB) is a fundamental structure that protects the composition of brain by determining which ions, metabolites, and nutrients are allowed to enter from blood or leave it towards circulation. BBB structurally composed layer capillary endothelial cells (BCECs) bound each other through tight junctions (TJs). However, its development as well maintenance properties controlled contact BCECs: pericytes, glial cells, even neurons themselves. Astrocytes seem, in particular, have very important role controlling most BBB. Here, we will focus on these latter since comprehension their roles physiology has been continuously expanding, including ability participate neurotransmission complex functions such learning memory. Accordingly, pathological conditions alter astrocytic can BBB's integrity, thus compromising many activities. In this review, also refer different kinds vitro models used study properties, evidencing modifications under conditions.

Язык: Английский

---

Ischemic brain edema: Emerging cellular mechanisms and therapeutic approaches

Neurobiology of Disease, Год журнала: 2023, Номер 178, С. 106029 - 106029

Опубликована: Фев. 2, 2023

Brain edema is one of the most devastating consequences ischemic stroke. Malignant cerebral main reason accounting for high mortality rate large hemispheric strokes. Despite decades tremendous efforts to elucidate mechanisms underlying formation brain and search therapeutic targets, current treatments remain largely symptom-relieving rather than aiming stop progression edema. Recent preclinical research reveals novel cellular after ischemia reperfusion. Advancement in neuroimaging techniques also offers opportunities early diagnosis prediction malignant stroke patients rapidly adopt life-saving surgical interventions. As reperfusion therapies become increasingly used clinical practice, understanding how influences critical decision-making post-reperfusion management. In this review, we summarize these advances past decade on mechanisms, evaluation, prediction, intervention settings, provide insight into future treatment

Язык: Английский

---

Translatome analysis reveals microglia and astrocytes to be distinct regulators of inflammation in the hyperacute and acute phases after stroke

Glia, Год журнала: 2023, Номер 71(8), С. 1960 - 1984

Опубликована: Апрель 17, 2023

Abstract Neuroinflammation is a hallmark of ischemic stroke, which leading cause death and long‐term disability. Understanding the exact cellular signaling pathways that initiate propagate neuroinflammation after stroke will be critical for developing immunomodulatory therapies. In particular, precise mechanisms inflammatory in clinically relevant hyperacute period, hours have not been elucidated. We used RiboTag technique to obtain microglia astrocyte‐derived mRNA transcripts (4 h) acute (3 days) period as these two cell types are key modulators neuroinflammation. Microglia initiated rapid response at 4 h by adopting an profile associated with recruitment immune cells. The astrocyte was marked stress genes transcription factors, such Fos Jun , involved pro‐inflammatory TNF‐α. By 3 days, shift proliferative state astrocytes strengthen their response. days partially driven upregulation factors C/EBPβ Spi1 Rel comprise 25% upregulated factor‐target interactions. Surprisingly, few sex differences across all groups were observed. Expression log 2 fold data sequenced available on user‐friendly website researchers examine gene changes generate hypotheses targets. Taken together, our comprehensively describe astrocyte‐specific translatome identify initiating

Язык: Английский

---

The neurovasculature as a target in temporal lobe epilepsy

Brain Pathology, Год журнала: 2023, Номер 33(2)

Опубликована: Янв. 4, 2023

Abstract The blood–brain barrier (BBB) is a physiological maintaining specialized brain micromilieu that necessary for proper neuronal function. Endothelial tight junctions and specific transcellular/efflux transport systems provide protective against toxins, pathogens, immune cells. function critically supported by other cell types of the neurovascular unit, including pericytes, astrocytes, microglia, interneurons. dysfunctionality BBB hallmark neurological diseases, such as ischemia, tumors, neurodegenerative infections, autoimmune neuroinflammatory disorders. Moreover, dysfunction involved in epilepsy, disorder characterized spontaneously occurring seizures because abnormally synchronized activity. While resistance to antiseizure drugs aim reduce hyperexcitability remains clinical challenge, targeting neurovasculature epilepsy patients have not been explored. use novel imaging techniques permits early detection leakage epilepsy; however, detailed mechanistic understanding causes consequences compromise unknown. Here, we discuss current knowledge involvement temporal lobe with emphasis on therapeutic target.

Язык: Английский

---

A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets

Neuron, Год журнала: 2024, Номер 112(18), С. 3069 - 3088.e4

Опубликована: Июль 16, 2024

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of transcriptomic response TBI (334,376 cells) across clinically relevant models, sex, region, time as foundational step in molecularly deconstructing heterogeneity. Results were unique cell populations, regions, time, highlighting importance cell-level resolution. identify cell-specific targets previously unrecognized roles for microglial ependymal subtypes. Ependymal-4 was hub neuroinflammatory signaling. A distinct lineage shared features with disease-associated microglia at 24 h, persistent gene-expression changes microglia-4 even 6 months after contusional TBI, contrasting all other types mostly returned naive levels. Regional sexual dimorphism noted. CEREBRI, our searchable (https://shiny.crc.pitt.edu/cerebri/), identifies subtypes/molecular is leverageable platform future efforts diseases overlapping pathophysiology.

Язык: Английский

---

Crosstalk Among Glial Cells in the Blood–Brain Barrier Injury After Ischemic Stroke

Molecular Neurobiology, Год журнала: 2024, Номер 61(9), С. 6161 - 6174

Опубликована: Янв. 27, 2024

Язык: Английский

---

Application of stimuli-responsive nanomedicines for the treatment of ischemic stroke

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 11

Опубликована: Фев. 2, 2024

Ischemic stroke (IS) refers to local brain tissue necrosis which is caused by impaired blood supply the carotid artery or vertebrobasilar system. As second leading cause of death in world, IS has a high incidence and brings heavy economic burden all countries regions because its disability rate. In order effectively treat IS, large number drugs have been designed developed. However, most with good therapeutic effects confirmed preclinical experiments not successfully applied clinical treatment due low accumulation efficiency areas after systematic administration. an emerging strategy for stimuli-responsive nanomedicines made great progress precisely delivering site IS. By response specific signals, change their particle size, shape, surface charge structural integrity, enables enhanced drug delivery controlled release within tissue. This breakthrough approach only enhances but also mitigates side commonly associated thrombolytic neuroprotective drugs. review aims comprehensively summarize recent Furthermore, prospect provided look forward better development this field.

Язык: Английский

---

Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 24, 2024

Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of cellular composition early lesion. Here we present single cell resolution transcriptomics dataset acute infarction. Oligodendrocyte lineage cells and astrocytes range among most transcriptionally perturbed populations exhibit infarction- subtype-specific molecular signatures. Specifically, find infarction restricted proliferating oligodendrocyte precursor (OPCs), mature oligodendrocytes reactive astrocytes, exhibiting transcriptional commonalities in injury. OPCs are involved shared immuno-glial cross talk with stroke-specific myeloid cells. Within perilesional zone, osteopontin positive accumulate close proximity CD44

Язык: Английский

---