Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury DOI Creative Commons
Ivó H. Hernández, Mario Villa-González, Gerardo Martín-López

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1639 - 1639

Published: June 30, 2021

Ischemic stroke is the second cause of mortality and first long-term disability constituting a serious socioeconomic burden worldwide. Approved treatments include thrombectomy rtPA intravenous administration, which, despite their efficacy in some cases, are not suitable for great proportion patients. Glial cell-related therapies progressively overcoming inefficient neuron-centered approaches preclinical phase. Exploiting ability microglia to naturally switch between detrimental protective phenotypes represents promising therapeutic treatment, similar way what happens with astrocytes. However, duality present many roles these cells upon ischemia poses notorious difficulty disentangling precise pathways target. Still, promoting M2/A2 microglia/astrocyte inhibiting M1/A1 neurotoxic profiles globally rendering results different vivo models stroke. On other hand, described oligodendrogenesis after brain seems be strictly beneficial, although less studied players paradigm negative effects could oligodendrocytes next years. Here, we review recent advances understanding role mentioned glial cell types main pathological events ischemic stroke, including inflammation, blood barrier integrity, excitotoxicity, reactive oxygen species management, metabolic support, neurogenesis, among others, special attention tested approaches.

Language: Английский

Neuroprotective Strategies for Ischemic Stroke—Future Perspectives DOI Open Access
Matteo Haupt, Stefan T. Gerner, Mathias Bähr

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4334 - 4334

Published: Feb. 22, 2023

Ischemic stroke is the main cause of death and most common acquired physical disability worldwide. Recent demographic changes increase relevance its sequelae. The acute treatment for restricted to causative recanalization restoration cerebral blood flow, including both intravenous thrombolysis mechanical thrombectomy. Still, only a limited number patients are eligible these time-sensitive treatments. Hence, new neuroprotective approaches urgently needed. Neuroprotection thus defined as an intervention resulting in preservation, recovery, and/or regeneration nervous system by interfering with ischemic-triggered cascade. Despite numerous preclinical studies generating promising data several agents, successful bench-to-bedside translations still lacking. present study provides overview current research field treatment. Aside from "traditional" drugs focusing on inflammation, cell death, excitotoxicity, stem-cell-based methods also considered. Furthermore, prospective method using extracellular vesicles that secreted various stem sources, neural cells bone marrow cells, given. review concludes short discussion microbiota-gut-brain axis may serve potential target future therapies.

Language: Английский

Citations

98
Crosstalk Between the Oxidative Stress and Glia Cells After Stroke: From Mechanism to Therapies DOI Creative Commons

Ganggui Zhu,

Xiaoyu Wang, Luxi Chen

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 25, 2022

Stroke is the second leading cause of global death and characterized by high rates mortality disability. Oxidative stress accompanied other pathological processes that together lead to secondary brain damage in stroke. As major component brain, glial cells play an important role normal development injury processes. Multiple connections exist pathophysiological changes reactive oxygen species (ROS) metabolism glia cell activation. Astrocytes microglia are rapidly activated after stroke, generating large amounts ROS via mitochondrial NADPH oxidase pathways, causing oxidative themselves neurons. Meanwhile, alterations morphology function, mediate their processes, such as neuroinflammation, excitotoxicity, blood-brain barrier damage. In contrast, protect Central Nervous System (CNS) from synthesizing antioxidants regulating Nuclear factor E2-related 2 (Nrf2) pathway, among others. Although numerous previous studies have focused on immune function cells, little attention has been paid stress. this paper, we discuss adverse consequences production oxidative-antioxidant imbalance addition, further describe biological potential therapeutic tools based cells.

Language: Английский

Citations

90
The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review DOI Creative Commons
Jinsong Zeng, Tingting Bao, Kailin Yang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 2, 2023

Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms IS. In particular, early proinflammatory response resulting from overactivation resident microglia infiltration circulating monocytes macrophages brain after cerebral ischemia leads to secondary injury. Microglia are innate immune cells that constantly monitor microenvironment under normal conditions. Once occurs, activated produce dual effects neurotoxicity neuroprotection, balance two determines fate damaged neurons. The activation defined as classical (M1 type) or alternative (M2 type). M1 type secrete pro-inflammatory cytokines neurotoxic mediators exacerbate neuronal damage, while M2 promote a repairing anti-inflammatory response. Fine regulation M1/M2 microglial minimize damage maximize protection has therapeutic value. This review focuses on interaction between other involved IS phenotypic characteristics, mechanism natural plant components regulating IS, providing novel candidate drugs for drug development.

Language: Английский

Citations

78
Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity DOI Creative Commons
Yaling Hu, Kelei Cao, Fang Wang

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(12), P. 1756 - 1774

Published: Dec. 19, 2022

Microglia continuously survey the brain parenchyma and actively shift status following stimulation. These processes demand a unique bioenergetic programme; however, little is known about metabolic determinants in microglia. By mining large datasets generating transgenic tools, here we show that hexokinase 2 (HK2), most active isozyme associated with mitochondrial membrane, selectively expressed microglia brain. Genetic ablation of HK2 reduced microglial glycolytic flux energy production, suppressed repopulation, attenuated surveillance damage-triggered migration male mice. elevation prominent immune-challenged or disease-associated In ischaemic stroke models, deletion promoted neuroinflammation potentiated cerebral damages. The enhanced inflammatory responses after are aberrant function reactive oxygen species accumulation. Our study demonstrates gates both activity to shape functions, changes which contribute abnormalities maladaptive inflammation diseases. Hu et al. role metabolism function, its dual under physiological pathological conditions mouse model stroke-induced

Language: Английский

Citations

76
Neutrophil Membrane‐Camouflaged Polyprodrug Nanomedicine for Inflammation Suppression in Ischemic Stroke Therapy DOI

Ya Zhao,

Qian Li,

Jing-Yan Niu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: March 23, 2024

Abstract Neuroinflammation has emerged as a major concern in ischemic stroke therapy because it exacebates neurological dysfunction and suppresses recovery after ischemia/reperfusion. Fingolimod hydrochloride (FTY720) is an FDA‐approved anti‐inflammatory drug which exhibits potential neuroprotective effects brain parenchyma. However, delivering sufficient amount of FTY720 through the blood–brain barrier into lesions without inducing severe cardiovascular side remains challenging. Here, neutrophil membrane‐camouflaged polyprodrug nanomedicine that can migrate tissues situ release response to elevated levels reactive oxygen species. This delivers 15.2‐fold more significantly reduces risk cardiotoxicity infection compared with intravenously administered free drug. In addition, single‐cell RNA‐sequencing analysis identifies attenuates poststroke inflammation by reprogramming microglia toward phenotypes, realized via modulating Cebpb‐regulated activation NLRP3 inflammasomes secretion CXCL2 chemokine. study offers new insights design fabrication nanomedicines for effective suppression therapy.

Language: Английский

Citations

38
Circadian rhythm regulates the function of immune cells and participates in the development of tumors DOI Creative Commons

Yuen Zeng,

Zichan Guo, Mengqi Wu

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 27, 2024

Abstract Circadian rhythms are present in almost all cells and play a crucial role regulating various biological processes. Maintaining stable circadian rhythm is essential for overall health. Disruption of this can alter the expression clock genes cancer-related genes, affect many metabolic pathways factors, thereby affecting function immune system contributing to occurrence progression tumors. This paper aims elucidate regulatory effects BMAL1, other on cells, reveal molecular mechanism rhythm’s involvement tumor its microenvironment regulation. A deeper understanding has potential provide new strategies treatment cancer immune-related diseases.

Language: Английский

Citations

35
Bioactivities of morroniside: A comprehensive review of pharmacological properties and molecular mechanisms DOI
Md. Shimul Bhuia, Raihan Chowdhury, Iffat Ara

et al.

Fitoterapia, Journal Year: 2024, Volume and Issue: 175, P. 105896 - 105896

Published: March 11, 2024

Language: Английский

Citations

18
Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion DOI Open Access
Tingjun Chen, Vanda A. Lennon, Yong Liu

et al.

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: unknown

Published: June 21, 2020

Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation cytolytic complement has been implicated as major effector tissue destruction that secondarily involves myelin. We investigated early precytolytic events in evolving pathophysiology NMO mice continuously infusing (NMO patient serum–derived or AQP4-specific mouse monoclonal), without exogenous complement, into spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were dose dependent, AQP4 and, unexpectedly, microglia dependent. In vivo cord imaging revealed striking physical interaction between astrocytes required signaling from C3a fragment their upregulated C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk involving early-activated CNS-intrinsic components microglial receptor appears be critical driver phase lesion, including initial motor impairment. Our results indicate merit consideration potential target for therapeutic intervention.

Language: Английский

Citations

122
Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice DOI Creative Commons
Jiyun Peng, Yong Liu, Anthony D. Umpierre

et al.

Molecular Brain, Journal Year: 2019, Volume and Issue: 12(1)

Published: Aug. 19, 2019

The P2Y12 receptor (P2Y12R) is a purinoceptor that selectively expressed in microglia the central nervous system. As signature receptor, microglial P2Y12R mediates process chemotaxis towards ADP/ATP gradients and engaged several neurological diseases including chronic pain, stroke seizures. However, role of regulating neuronal excitability innate behaviors not fully understood. Here, we generated P2Y12-floxed mice to delete beginning development (CX3CR1Cre/+:P2Y12f/f; "constitutive knockout"), or after normal adult (CX3CR1CreER/+:P2Y12f/f; "induced knockout"). Using battery behavioral tests, found both constitutive induced knockout exhibited fear but learned behaviors. After were exposed elevated plus maze, c-fos expression ventral hippocampus CA1 neurons was robustly increased compared with wild-type mice. Consistently, using whole cell patch clamp recording, results suggest regulates developing

Language: Английский

Citations

114
Microglial depletion aggravates the severity of acute and chronic seizures in mice DOI Creative Commons
Wen‐Ning Wu, Yujiao Li,

Yujia Wei

et al.

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 89, P. 245 - 255

Published: July 1, 2020

Microglia are the resident immune cells of center nervous system and participate in various neurological diseases. Here we determined function microglia epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1

Language: Английский

Citations

105