Microglia at the blood brain barrier in health and disease

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 13, 2024

The blood brain barrier (BBB) plays a crucial role in maintaining homeostasis by selectively preventing the entry of substances from peripheral into central nervous system (CNS). Comprised endothelial cells, pericytes, and astrocytes, this highly regulated encompasses majority brain’s vasculature. In addition to its protective function, BBB also engages significant crosstalk with perivascular macrophages (MΦ) microglia, resident MΦ brain. These interactions play pivotal modulating activation state cells comprising BBB, as well MΦs themselves. Alterations systemic metabolic inflammatory states can promote cell dysfunction, reducing integrity potentially allowing factors leak CNS compartment. This may mediate MΦs, initiate further immune responses within parenchyma, suggesting neuroinflammation be triggered signaling periphery, without primary injury or disease originating CNS. intricate interplay between periphery through highlights importance understanding microglia mediating challenges. Despite recent advancements, our is still early stages, leaving gap knowledge. However, emerging research shedding light on involvement at various conditions, including infections, diabetes, ischemic stroke. review aims provide comprehensive overview current investigating relationship health disease. By exploring these connections, we hope advance challenges their impact pathology. Uncovering hold promise for development novel therapeutic strategies neurological conditions that involve vascular mechanisms.

Язык: Английский

---

Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia–reperfusion injury

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Март 21, 2024

Abstract Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates secretion release activates neuroinflammation, aggravating I/R injury. However, cellular sources MPO/HOCl ischemic brain are unclear yet. Whether HOCl could promote remains unknown. In present study, we investigated roles microglia-derived mediating translocation secretion, damage blood-brain barrier (BBB) disruption vitro, under co-culture conditions with microglia BV cells but not single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased expression PC12 cells. After were exposed to OGD/R, MPO-containing exosomes derived from BV2 released transferred cells, increasing The promoted aggravated OGD/R-induced apoptosis. vivo, SD rats subjected 2 h middle artery occlusion (MCAO) plus different periods reperfusion. Increased production was observed at reperfusion stage, accomplished enlarged infarct volume, BBB neurological dysfunctions. Treatment MPO inhibitor 4-aminobenzoic hydrazide (4-ABAH) scavenger taurine reversed those changes. colocalized cytoplasm HMGB1, which blocked by rat I/R-injured brain. We finally performed a clinical investigation found that plasma concentration positively correlated volume deficit scores stroke patients. Taken together, conclude ischemia/hypoxia activate transfer adjacent for production; Subsequently, mediate aggravates Furthermore, level be novel biomarker indexing

Язык: Английский

---

Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation

Stroke and Vascular Neurology, Год журнала: 2025, Номер unknown, С. svn - 003442

Опубликована: Фев. 24, 2025

Background Melatonin protects against ischaemic stroke in diabetic animal models, though the mechanisms involving brain and peripheral immune responses remain underexplored. We aimed to clarify how melatonin interacts with these protect mice. Methods Type 1 diabetes mellitus (T1DM) was induced mice using streptozotocin. RNA sequencing of tissue blood mononuclear cells (PBMCs) performed 24 hours poststroke. Inflammatory were evaluated 72 after ischaemia/reperfusion. Results reduced infarction improved neurological function T1DM In brain, downregulated inflammatory factor expression, bioinformatics identifying 62 differentially expressed genes (DEGs) related inflammation 11 associated inflammasomes. Western blotting confirmed reductions NLRP3, HMGB1 Cleaved Caspase-1 expression. Flow cytometry showed infiltration CD8+T neutrophils. decreased IL-6, IL-1β IL-4 levels. PBMCs, revealed 939 DEGs following treatment. Kyoto Encyclopaedia Genes Genomes analysis indicated that involved metabolic pathways, upregulated enriched Jak-STAT signalling pathway. GO cytosol, macromolecule modification. Protein–protein interaction affected 38 inflammation-associated linked key cytokines (Il6, Il1b, Ifng, Il4). increased cells, monocytes neutrophils blood, suggesting a reversal immunosuppression. Multiplex cytokine assays IL-6 IFN-γ Conclusion Poststroke therapy reduces damage by modulating central responses.

Язык: Английский

---

Role of Crosstalk between Glial Cells and Immune Cells in Blood-Brain Barrier Damage and Protection after Acute Ischemic Stroke

Aging and Disease, Год журнала: 2023, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2023

Blood-brain barrier (BBB) damage is the main pathological basis for acute ischemic stroke (AIS)-induced cerebral vasogenic edema and hemorrhagic transformation (HT). Glial cells, including microglia, astrocytes, oligodendrocyte precursor cells (OPCs)/oligodendrocytes (OLs) play critical roles in BBB protection. Recent evidence indicates that immune also have an important role damage, HT. Therefore, regulating crosstalk between glial would hold promise to alleviate AIS-induced damage. In this review, we first introduce of glia pericytes, protection after AIS, emphasizing polarization, inflammatory response other cells. We then describe cell-derived exosomes AIS. Next, specifically discuss Finally, propose could be a potential target alleviating AIS some molecular targets strategies by

Язык: Английский

---

The NG2-glia is a potential target to maintain the integrity of neurovascular unit after acute ischemic stroke

Neurobiology of Disease, Год журнала: 2023, Номер 180, С. 106076 - 106076

Опубликована: Март 13, 2023

The neurovascular unit (NVU) plays a critical role in health and disease. In the current review, we discuss of class neural/glial antigen 2 (NG2)-expressing glial cells (NG2-glia) regulating NVU after acute ischemic stroke (AIS). We first introduce NG2-glia formation during development as well aging-induced damage to accompanying change. then reciprocal interactions between other component NVU, emphasizing factors that could influence NG2-glia. Damage integrity is pathological basis edema hemorrhagic transformation, most dreaded complication AIS. AIS-induced effect transplantation on are summarized. next oligodendrogenesis white matter repair angiogenesis which associated with outcome patients Finally, review strategies promote proliferation differentiation propose use dental pulp stem (DPSC)-derived exosome promising strategy reduce injury through maintaining by endogenous differentiation.

Язык: Английский

---

Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 5, 2024

Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions cerebral I/R are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing a variety organs. However, systematic review covering all neuroprotective effects melatonin has not been reported yet. Thus, we perform comprehensive overview influence on by collecting available literature exploring latent effect as well stroke. In this review, outline extensive scientific studies and summarize beneficial functions melatonin, including reducing infarct volume, decreasing brain edema, improving neurological attenuating blood-brain barrier breakdown, its key protective mechanisms almost every aspect injury, inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity mitochondrial dysfunction. Subsequently, also predictive implications clinical studies. We hope that our can provide most introduction current advancements new insights into personalized diagnosis treatment

Язык: Английский

---

Melatonin as an Antioxidant Agent in Stroke: An Updated Review

Aging and Disease, Год журнала: 2022, Номер 13(6), С. 1823 - 1823

Опубликована: Янв. 1, 2022

Stroke is a devastating disease associated with high mortality and disability worldwide, generally classified as ischemic or hemorrhagic, which share certain similar pathophysiological processes. Oxidative stress critical factor involved in stroke-induced injury, not only directly damages brain tissue, but also enhances series of pathological signaling cascades, contributing to inflammation, edema, neuronal death. To alleviate these serious secondary injuries, neuroprotective agents targeting oxidative inhibition may serve promising treatment strategy. Melatonin hormone secreted by the pineal gland, has various properties, such antioxidation, anti-inflammation, circadian rhythm modulation, promotion tissue regeneration. Numerous animal experiments studying stroke have confirmed that melatonin exerts considerable effects, partially via anti-oxidative stress. In this review, we introduce possible role an antioxidant based on latest published studies clinical research.

Язык: Английский

---

CRTC1 is a potential target to delay aging-induced cognitive deficit by protecting the integrity of the blood-brain barrier via inhibiting inflammation

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2023, Номер 43(7), С. 1042 - 1059

Опубликована: Апрель 22, 2023

Aging can cause attenuation in the functioning of multiple organs, and blood-brain barrier (BBB) breakdown could promote occurrence disorders central nervous system during aging. Since inflammation is considered to be an important factor underlying BBB injury aging, vascular endothelial cell senescence serves as a critical pathological basis for destruction integrity. In current review, we have first introduced concepts related aging-induced cognitive deficit integrity damage. Thereafter, reviewed potential relationship between disruption cognition role inflammation, senescence, injury. We also briefly function CREB-regulated transcription co-activator 1 (CRTC1) CRTC1 changes well roles CRTC1/cyclooxygenase-2 (COX-2) regulating Finally, mechanisms been summarized propose that promising target delay by protecting through promoting inhibition inflammation-mediated senescence.

Язык: Английский

---

Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability

Acta Pharmacologica Sinica, Год журнала: 2024, Номер 45(11), С. 2241 - 2252

Опубликована: Июнь 20, 2024

Язык: Английский

---

Melatonin modulates the aggravation of pyroptosis, necroptosis, and neuroinflammation following cerebral ischemia and reperfusion injury in obese rats

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1869(7), С. 166785 - 166785

Опубликована: Июнь 9, 2023

Язык: Английский

---