Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2563 - 2563

Published: Feb. 22, 2024

Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding tissue. While lower-grade gliomas present more circumscribed borders, high-grade aggressive with widespread infiltration and dissemination. Glioblastoma (GBM) known for its high invasiveness association poor prognosis. Its low survival rate due to certainty recurrence, caused microscopic which makes surgical eradication unattainable. New insights GBM biology at single-cell level have enabled identification mechanisms exploited glioma cells invasion. In this review, we explore current understanding several molecular pathways used tumor invade normal We address intrinsic biological drivers cell invasion, tackling how interact each other microenvironment (TME). focus on recently discovered neuronal niche in TME, including local as well distant neurons, contributing growth then promoted astrocytes immune cells. Finally, review literature therapeutic targeting

Language: Английский

---

Ultrasound‐Activated Piezoelectric Nanoparticles Trigger Microglia Activity Against Glioblastoma Cells

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(18)

Published: March 21, 2024

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug-resistant progression. GBM "builds" around its primary core genetically heterogeneous tumor-microenvironment (TME), recruiting surrounding healthy cells releasing various intercellular signals. Glioma-associated microglia (GAM) represent largest population of collaborating cells, which, in TME, usually exhibit anti-inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth. Conversely, "classically activated" M1 could provide proinflammatory antitumorigenic activity, expected to exert beneficial effect defeating glioblastoma. In this work, immunotherapy approach based on modulation GAM phenotype proposed, through controlled localized electrical stimulation. The developed strategy relies wireless ultrasonic excitation polymeric piezoelectric nanoparticles coated with cell membrane extracts, exploit homotypic targeting antiglioma applications. Such camouflaged nanotransducers locally generate cues membranes, activating their ultimately triggering promising anticancer activity. Collected findings open new perspectives immune activities "smart" nanomaterials and, more specifically, innovative auspicious tool glioma immunotherapy.

Language: Английский

---

Inflammatory Pathogenesis of Post-stroke Depression

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Post-stroke depression (PSD) is a complex mood disorder that emerges in individuals following stroke, characterized by the development of depressive symptoms. The pathogensis PSD diverse, with inflammation playing vital role its onset and progression. Emerging evidence suggests microglial activation, astrocyte responses, nuclear factor κB(NF-κB) signaling, dysregulation hypothalamic pituitary adrenal (HPA) axis, alterations brain-derived neurotrophic (BDNF) expression, neurotransmitter imbalances, adenosine triphosphate (ATP) receptors oxidative stress are intricately linked to pathogenesis PSD. involvement inflammatory cytokines these processes highlights significance pathway. Integrating hypotheses, mechanism offers novel perspective expand therapeutic strategies for

Language: Английский

---

The Alteration of Microglial Calcium Homeostasis in Central Nervous System Disorders: A Comprehensive Review

Neuroglia, Journal Year: 2024, Volume and Issue: 5(4), P. 410 - 444

Published: Oct. 21, 2024

Microglia, the unique and motile immune cells of central nervous system (CNS), function as a security guard in maintaining CNS homeostasis, primarily through calcium signaling. The dynamics microglia control important functions such phagocytosis, cytokine release, migration. Calcium dysregulation has been linked to several disorders, like Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS), ischemic stroke (IS). entering channels voltage-gated (VGCCs), store-operated entry (SOCE), transient receptor potential (TRP) is essential for microglial activation pro-inflammatory responses. Under pathological conditions, formation amyloid-β plaques AD, aggregation α-synuclein PD, oxidative stress MS, exacerbates neuroinflammation, mitochondrial dysfunction, neurodegeneration. Therapeutic strategies targeting signaling pathways, using channel blockers antioxidant interventions, show promise alleviating slowing down progression. This review summarizes underlying mechanisms therapeutic benefits restoring balance disorders.

Language: Английский

---

Mesenchymal stem cell-derived exosomes regulate microglia phenotypes: a promising treatment for acute central nervous system injury

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 0(0), P. 0 - 0

Published: Jan. 1, 2022

There is growing evidence that long-term central nervous system (CNS) inflammation exacerbates secondary deterioration of brain structures and functions one the major determinants disease outcome progression. In acute CNS injury, microglia are among first cells to respond play a critical role in neural repair regeneration. However, microglial activation can also impede amplify tissue damage, phenotypic transformation may be responsible for this dual role. Mesenchymal stem cell (MSC)-derived exosomes (Exos) promising therapeutic agents treatment injuries due their immunomodulatory regenerative properties. MSC-Exos nanoscale membrane vesicles actively released by used clinically as circulating biomarkers diagnosis prognosis. neuroprotective several models, including stroke traumatic showing great clinical potential. This review summarized classification injury disorders discussed prominent specific regulating pro-inflammatory neuroinflammatory following injury. Finally, explored potential mechanisms factors associated with modulating balance microglia, focusing on interplay between inflammation, brain, aspects, an emphasis strategies interventions improving functional recovery from early caused

Language: Английский

---

Current Chemical, Biological, and Physiological Views in the Development of Successful Brain-Targeted Pharmaceutics

Neurotherapeutics, Journal Year: 2022, Volume and Issue: 19(3), P. 942 - 976

Published: April 1, 2022

Language: Английский

---

The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner

PLoS Biology, Journal Year: 2022, Volume and Issue: 20(1), P. e3001526 - e3001526

Published: Jan. 27, 2022

The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, main inflammatory cells brain, has remained unclear date. Therefore, we generated a novel transgenic mouse line which microglial was deleted. We show that shapes both baseline and reactive microglia morphology, process recruitment site injury, adaptation changes cellular volume cell-autonomous manner via regulating membrane conductance. In addition, deficiency results NLRP3 inflammasome priming increased production interleukin-1β (IL-1β), rendering prone exaggerated responses. with this, central (intracortical) administration blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. contrast, systemic bumetanide application decreased inflammation brain. Microglial KO animals exposed experimental stroke showed significantly brain inflammation, cerebral edema worse outcome. Thus, emerges as an important player controlling homeostasis responses through modulate injury. contribution actions is likely be relevant for disorders.

Language: Английский

---

Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

Cerebrovascular diseases and their sequalae, such as ischemic stroke, chronic cerebral hypoperfusion, vascular dementia are significant contributors to adult disability cognitive impairment in the modern world. Astrocytes an integral part of neurovascular unit CNS play a pivotal role homeostasis, including ionic p H balance, neurotransmission, blood flow, metabolism. respond insults, inflammation, through unique molecular, morphological, functional changes, collectively known reactive astrogliosis. The function astrocytes has been subject debate. Initially, were thought primarily supportive maintaining structure nervous system. However, recent studies suggest that may have both beneficial detrimental effects. For example, can cause oligodendrocyte death demyelination. In this review, we will summarize (1) roles ion transporter cascade astrogliosis, (2) related dementias, (3) potential therapeutic approaches for dementing disorders targeting astrocytes. Understanding relationship between cascade, cerebrovascular reveal mechanisms targets development therapies brain associated with

Language: Английский

---

Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Dec. 8, 2022

Abstract The hippocampus is a plastic brain area that shows functional segregation along its longitudinal axis, reflected by higher level of long-term potentiation (LTP) in the CA1 region dorsal (DH) compared to ventral (VH), but mechanisms underlying this difference remain elusive. Numerous studies have highlighted importance microglia–neuronal communication modulating synaptic transmission and hippocampal plasticity, although role physiological contexts still largely unknown. We characterized depth features microglia two poles investigated their contribution plasticity under conditions. unveiled influence differentially amplitude LTP DH VH, showing minocycline or PLX5622 treatment reduced DH, while increasing it VH. This was recapitulated Cx3cr1 knockout mice, indicating key setting conditions for processes region-specific manner, CX3CL1–CX3CR1 pathway element determining basal regions. observed differences at were associated with transcriptional changes expression genes encoding Il-1 , Tnf-α Il-6 Bdnf essential players neuronal plasticity. Furthermore, SR showed an increase soma more extensive arborization, increased prevalence immature lysosomes accompanied elevation mRNA phagocytic markers Mertk Cd68 surge microglial outward K + currents VH suggesting distinct phenotypic state across poles. Overall, we molecular, morphological, ultrastructural, profile poles, modifications subregions related different statuses can contribute dissect phenotypical aspects many diseases which are known be involved.

Language: Английский

---

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(7), P. 1799 - 1799

Published: June 23, 2023

Neuropathic pain is a debilitating condition characterized by abnormal signaling within the nervous system, resulting in persistent and often intense sensations of pain. It can arise from various causes, including traumatic nerve injury, neuropathy, certain diseases. We present an overview current emerging pharmacotherapies for neuropathic pain, focusing on novel drug targets potential therapeutic agents. Current pharmacotherapies, tricyclic antidepressants, gabapentinoids, serotonin norepinephrine re-uptake inhibitors, are discussed, as treatments, such ambroxol, cannabidiol, N-acetyl-L-cysteine. Additionally, article highlights need further research this field to identify new develop more effective targeted therapies management.

Language: Английский

---