IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice DOI Creative Commons
Myrto Andreadou, Florian Ingelfinger, Donatella De Feo

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(10), P. 1701 - 1712

Published: Sept. 25, 2023

Abstract Interleukin-12 (IL-12) is a potent driver of type 1 immunity. Paradoxically, in autoimmune conditions, including the CNS, IL-12 reduces inflammation. The underlying mechanism behind these opposing properties and involved cellular players remain elusive. Here we map receptor (IL-12R) expression to NK T cells as well neurons oligodendrocytes. Conditionally ablating IL-12R across cell types adult mice assessing their susceptibility experimental encephalomyelitis revealed that neuroprotective role mediated by neuroectoderm-derived cells, specifically neurons, not immune cells. In human brain tissue from donors with multiple sclerosis, observe an distribution comparable mice, suggesting similar mechanisms humans. Combining flow cytometry, bulk single-nucleus RNA sequencing, reveal IL-12-induced adaption preventing early neurodegeneration sustaining trophic factor release during neuroinflammation, thereby maintaining CNS integrity mice.

Language: Английский

Co-transplantation of autologous Treg cells in a cell therapy for Parkinson’s disease DOI
Tae Yoon Park, Jeha Jeon, Nayeon Lee

et al.

Nature, Journal Year: 2023, Volume and Issue: 619(7970), P. 606 - 615

Published: July 12, 2023

Language: Английский

Citations

64
Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration DOI Creative Commons
Stanisław Szlufik,

Kamila Kopeć,

Stanisław Szleszkowski

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 286 - 286

Published: Feb. 5, 2024

The key to the effective treatment of neurodegenerative disorders is a thorough understanding their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment glymphatic system function in neurodegeneration contributes progression pathological question arises as how related. This review highlights direct indirect influence these two seemingly independent Protein aggregates, characteristic feature neurodegeneration, correlated with clearance neuroinflammation. Glial cells cannot be overlooked when considering neuroinflammatory Astrocytes essential for functioning play crucial role inflammatory responses central nervous system. It imperative acknowledge significance AQP4, protein that exhibits high degree polarization astrocytes AQP4 influences processes have not yet been clearly delineated. Another interesting issue gut–brain axis microbiome, which potentially impact discussed A discussion correlation between may contribute exploring pathomechanism neurodegeneration.

Language: Английский

Citations

16
Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches DOI Creative Commons

Dmitriy Lapin,

Archna Sharma, Ping Wang

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 21, 2025

Abstract Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS is comprised primary secondary injury. Inflammatory incited by damage-associated molecular patterns (DAMPs) which signal variety resident cells infiltrating immune cells. Extracellular cold-inducible RNA-binding protein (eCIRP) DAMP acts through multiple non-immune to promote inflammation. Despite the well-established role eCIRP in systemic sterile inflammation, its less elucidated. Recent literature suggests that pleiotropic inflammatory mediator also being evaluated clinical biomarker indicate prognosis injuries. This review provides broad overview injury, with focus on immune-mediated neuroinflammation. We then what known about mechanisms both non-CNS cells, identifying opportunities for further study. explore eCIRP’s potential prognostic marker severity outcome. Next, we provide an eCIRP-targeting therapeutics suggest strategies develop these agents ameliorate Finally, emphasize exploring novel mechanisms, aside from neuroinflammation, critical therapeutic target

Language: Английский

Citations

2
Nasal anti-CD3 monoclonal antibody ameliorates traumatic brain injury, enhances microglial phagocytosis and reduces neuroinflammation via IL-10-dependent Treg–microglia crosstalk DOI Creative Commons
Saef Izzy,

Taha Yahya,

Omar Albastaki

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Neuroinflammation plays a crucial role in traumatic brain injury (TBI), contributing to both damage and recovery, yet no effective therapy exists mitigate central nervous system (CNS) promote recovery after TBI. In the present study, we found that nasal administration of an anti-CD3 monoclonal antibody ameliorated CNS behavioral deficits mouse model contusional Nasal induced population interleukin (IL)-10-producing regulatory T cells (Treg cells) migrated closely contacted microglia. Treg directly reduced chronic microglia inflammation regulated their phagocytic function IL-10-dependent manner. Blocking IL-10 receptor globally or specifically on vivo abrogated beneficial effects anti-CD3. However, adoptive transfer IL-10-producing TBI-injured mice restored these by enhancing microglial capacity reducing microglia-induced neuroinflammation. These findings suggest represents promising new therapeutic approach for treating TBI potentially other forms acute injury. shows promise neuroinflammation aiding mice. It induces interleukin-10-producing enhance activity reduce inflammation, repair.

Language: Английский

Citations

2
Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases DOI Creative Commons
Miaomiao Chen,

Xing-Ning Lai,

Xifeng Wang

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: Oct. 5, 2021

Microglia and astrocytes maintain tissue homeostasis in the nervous system. Both microglia have pro-inflammatory phenotype anti-inflammatory phenotype. Activated activated can contribute to several neurological diseases. Long non-coding RNAs (lncRNAs) circular (circRNAs), two groups of (ncRNAs), function as competing endogenous (ceRNAs) impair microRNA (miRNA) inhibition on targeted messenger (mRNAs). LncRNAs circRNAs are involved various disorders. In this review, we summarized that lncRNAs participate dysfunction, astrocyte neuron damage, inflammation. Thereby, positively or negatively regulate diseases, including spinal cord injury (SCI), traumatic brain (TBI), ischemia-reperfusion (IRI), stroke, neuropathic pain, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), Alzheimer’s (AD). Besides, also found a lncRNA/circRNA-miRNA-mRNA regulatory network mediated Through hope cast light mechanisms diseases provide new insights for treatment.

Language: Английский

Citations

80
Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury DOI Creative Commons

Pengju Wei,

Ke Wang, Chen Luo

et al.

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: June 15, 2021

The secondary injury caused by traumatic brain (TBI), especially white matter (WMI), is highly sensitive to neuroinflammation, which further leads unfavored long-term outcomes. Although the cross-talk between three active events, immune cell infiltration, BBB breakdown, and proinflammatory microglial/macrophage polarization, plays a role in vicious cycle, its mechanisms are not fully understood. It has been reported that cordycepin, an extract from Cordyceps militaris, can inhibit TBI-induced neuroinflammation although effects of cordycepin remain unknown. Here, we report our investigation cordycepin's neuroprotective function underlying immunological mechanism.TBI mice model was established with controlled cortical impact (CCI) method. Cordycepin intraperitoneally administered twice daily for week. Neurological outcomes were assessed behavioral tests, including grid walking test, cylinder wire hang rotarod test. Immunofluorescence staining, transmission electron microscopy, electrophysiology recording employed assess histological functional lesions. Quantitative-PCR flow cytometry used detect neuroinflammation. tracers Sulfo-NHS-biotin Evans blue blood-brain barrier (BBB) leakage. Western blot gelatin zymography analyze protein activity or expression. Neutrophil depletion vivo performed via using Ly6G antibody intraperitoneal injection.Cordycepin administration ameliorated neurological deficits reduced neuronal tissue loss TBI mice. Meanwhile, integrity also preserved, revealed multiple dimensions, such as morphology, histology, ultrastructure, electrical conductivity. inhibited microglia/macrophage pro-inflammatory polarization promoted anti-inflammatory after TBI. breach attenuated at 3 days suppressed activities MMP-2 MMP-9 neutrophil infiltration Moreover, provided cordycepin-like effect, united did show benefit superposition.The suppressing TBI, thereby preserving changing polarization. These findings provide significant clinical potentials improve quality life patients.

Language: Английский

Citations

72
Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside DOI Creative Commons
Daniela Baracaldo-Santamaría, Daniel Felipe Ariza-Salamanca, María Gabriela Corrales-Hernández

et al.

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(1), P. 152 - 152

Published: Jan. 8, 2022

Traumatic brain injury (TBI) is one of the leading causes morbidity and mortality. Consequences vary from mild cognitive impairment to death and, no matter severity subsequent sequelae, it represents a high burden for affected patients health care system. Brain trauma can cause neuronal through mechanical forces that disrupt cell architecture, other secondary consequences mechanisms such as inflammation, oxidative stress, programmed death, most importantly, excitotoxicity. This review aims provide comprehensive understanding many classical novel pathways implicated in tissue damage following TBI. We summarize preclinical evidence potential therapeutic interventions describe available clinical evaluation drug targets vitamin B12 ifenprodil, among others.

Language: Английский

Citations

69
Inflammasome activation in traumatic brain injury and Alzheimer's disease DOI Creative Commons
Nathan H. Johnson, Juan Pablo de Rivero Vaccari, Helen M. Bramlett

et al.

Translational research, Journal Year: 2022, Volume and Issue: 254, P. 1 - 12

Published: Sept. 6, 2022

Language: Английский

Citations

51
Early posttraumatic CSF1R inhibition via PLX3397 leads to time- and sex-dependent effects on inflammation and neuronal maintenance after traumatic brain injury in mice DOI Creative Commons
Yong Wang,

Isa Wernersbach,

Jenny Strehle

et al.

Brain Behavior and Immunity, Journal Year: 2022, Volume and Issue: 106, P. 49 - 66

Published: Aug. 3, 2022

There is a need for early therapeutic interventions after traumatic brain injury (TBI) to prevent neurodegeneration. Microglia/macrophage (M/M) depletion and repopulation treatment with colony stimulating factor 1 receptor (CSF1R) inhibitors reduces The present study investigates short- long-term consequences CSF1R inhibition during the phase TBI.Sex-matched mice were subjected TBI by PLX3397 5 days sacrificed at or 30 post (dpi). Neurological deficits monitored tissues examined histo- molecular pathological markers. RNAseq was performed dpi samples.At dpi, attenuated TBI-induced perilesional M/M increase associated gene expressions up 50%. attenuation did not affect structural damage this time-point, impaired hematoma clearance, had no effect on IL-1β expression. At following drug discontinuation repopulation, tissue loss regardless of sex, as well hippocampal atrophy thalamic neuronal in male mice. Selected markers inflammation apoptosis reduced males but increased females compared corresponding vehicle groups. outcome behaving almost affected. set enrichment analysis (GSEA) injured brains revealed more genes dendritic spines synapse function vehicle, suggesting improved maintenance recovery. In mice, GSEA showed high oxidative phosphorylation, oxidoreductase activity ribosomal biogenesis stress abundance metabolically highly active cells. More immune processes phagocytosis treated vs males, sex-specific differences response TBI.M/M via loss, improves fosters Overall effects there evidence that benefit than female

Language: Английский

Citations

46
Human Umbilical Cord Mesenchymal Stem Cells Derived Exosomes Promote Neurological Function Recovery in a Rat Spinal Cord Injury Model DOI
Jian Kang, Yan Guo

Neurochemical Research, Journal Year: 2022, Volume and Issue: 47(6), P. 1532 - 1540

Published: Feb. 8, 2022

Language: Английский

Citations

38