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

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery DOI Creative Commons
Sara Bernardo-Castro, João André Sousa, Ana Brás

et al.

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 9, 2020

The blood-brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting brain from unwanted compounds, but its impairment involved in vast number of pathological conditions. Disruption BBB and increase permeability are key development several neurological diseases have been extensively studied stroke. Ischemic stroke most prevalent type characterized by myriad events triggered an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). seems follow multiphasic pattern throughout different stages associated with distinct biological substrates. In hyperacute stage, sudden hypoxia damages BBB, leading cytotoxic edema increased permeability; acute neuroinflammatory response aggravates injury, higher consequent risk HT be motivated reperfusion therapy; subacute stage (1-3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky this has improved clinical recovery. chronic (>6 restoration factors leads start decreasing permeability. Nonetheless, will persist some degree weeks after injury. Understanding behind dysregulation pathophysiology could potentially help guide care decisions new therapeutic targets; however, effective translation into practice still lacking. review, we address physiological through ischemic their role

Language: Английский

Citations

292
Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions DOI Creative Commons
Csaba Cserép, Balázs Pósfai, Ádám Dénes

et al.

Neuron, Journal Year: 2020, Volume and Issue: 109(2), P. 222 - 240

Published: Dec. 2, 2020

Language: Английский

Citations

180
Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke: Applications for natural compounds from medicinal herbs DOI Open Access
Ting Zhu, Lei Wang, Liping Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 148, P. 112719 - 112719

Published: Feb. 12, 2022

Neuroprotective and neurorestorative therapy represent two major drug intervention strategies for ischemic stroke. Multiple factors such as excitotoxicity, inflammation, angiogenesis, neurogenesis are the main pathological processes that underlie acute chronic brain injury. Furthermore, their intimate interactions mediate blood-brain barrier permeability, increase neurovascular unit structural damage well a hemorrhagic transformation during We aimed to review current understandings of underlying mechanisms neuroprotection neurorestoration in Notably, traditional Chinese medicine (TCM) has notable advantages comprehensive treatment overall regulation multi-site multi-target diseases. Therefore, we reviewed recent advances natural compounds from medicinal herbs possess bioactivities simultaneously promoting (e.g., oxidative stress, apoptosis, autophagy) neurogenesis, axonal sprouting) following ischemia These were divided into glycosides (astragaloside IV, gastrodin, ginsenoside Rg1 salidroside), flavonoids (baicalin, icariin, puerarin breviscapine), phenols (resveratrol, curcumin salvianolic acid B), terpenes (ginkgolide B catalpol). found all exhibited anti-brain activities vivo vitro experiments by and, or neurorestoration. This tracks summarizes progress past five years explore active molecular TCMs produce pro-neuroprotection pro-neurorestoration. Additionally, provide another basis reference supporting TCMs, which could ultimately lead development precise clinical medications stroke treatment.

Language: Английский

Citations

178
mTOR‐mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP DOI
Yaling Hu,

Weihao Mai,

Lunhao Chen

et al.

Glia, Journal Year: 2019, Volume and Issue: 68(5), P. 1031 - 1045

Published: Dec. 3, 2019

Abstract Microglia constantly survey the brain microenvironment and rapidly adopt different phenotypes in response to environmental stimuli. Such dynamic functions require a unique metabolism bioenergetics. However, little is known about basic of microglia how metabolic changes regulate function. Here, we uncover that activation accompanied by extensive transcriptional glucose lipid metabolism‐related genes. Using flux assays, found LPS, prototype pathogen‐associated molecular patterns (PAMPs), significantly enhanced glycolysis but suppressed oxidative phosphorylation (OXPHOS) primary cultured microglia. By contrast, ATP, damage‐associated pattern (DAMPs) triggers sterile microglia, boosted both OXPHOS. Importantly, LPS ATP activated mechanistic target rapamycin (mTOR) pathway intracellular reactive oxygen species (ROS). Inhibition mTOR activity ROS production conditions exerted effects on OXPHOS: it attenuated ATP‐induced elevation OXPHOS, yet had no impact LPS‐induced suppression Further, inhibition or decreased proinflammatory cytokines tumor necrosis factor‐α (TNF‐α) derived neurotrophic factor (BDNF) Our study reveals critical role for regulation programming shape their distinct under states shed light potential application targeting interfere with microglia‐mediated neuroinflammation multiple disorders.

Language: Английский

Citations

170
Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke DOI Creative Commons

Rui Mao,

Ningning Zong,

Yujie Hu

et al.

Neuroscience Bulletin, Journal Year: 2022, Volume and Issue: 38(10), P. 1229 - 1247

Published: May 5, 2022

Abstract Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase thrombectomy. Even so, patients still benefit little due short therapeutic window risk of ischemia/reperfusion injury. It is therefore urgent figure out neuronal death mechanisms following ischemic in order develop new neuroprotective strategies. Regarding pathogenesis, multiple pathological events trigger activation cell pathways. Particular attention should be devoted excitotoxicity, oxidative stress, inflammatory responses. Thus, this article, we first review principal underlying mediated these significant events, such as intrinsic extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, autophagic death. Then, further discuss possibility interventions targeting summarize present pharmacological achievements.

Language: Английский

Citations

165
Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage DOI
Yang Cao,

Yin Li,

Chao He

et al.

Neuroscience Bulletin, Journal Year: 2021, Volume and Issue: 37(4), P. 535 - 549

Published: Jan. 9, 2021

Language: Английский

Citations

148
Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke DOI Open Access
Adjanie Patabendige, Ayesha Singh, Stuart I. Jenkins

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(8), P. 4280 - 4280

Published: April 20, 2021

Transient or permanent loss of tissue perfusion due to ischaemic stroke can lead damage the neurovasculature, and disrupt brain homeostasis, causing long-term motor cognitive deficits. Despite promising pre-clinical studies, clinically approved neuroprotective therapies are lacking. Most studies have focused on neurons while ignoring important roles other cells neurovascular unit, such as astrocytes pericytes. Astrocytes for development maintenance blood–brain barrier, structural support, control cerebral blood flow secretion factors. Emerging data suggest that astrocyte activation exerts both beneficial detrimental effects following stroke. Activated provide neuroprotection contribute neurorestoration, but also secrete inflammatory modulators, leading aggravation lesion. more resistant than cell types pathology, exert a regulative effect in response ischaemia. These remain incompletely understood, though they represent an appealing target protection In this review, we summarise astrocytic contributions repair stroke, explore mechanisms promote revascularisation which may be targeted developing novel

Language: Английский

Citations

145
Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system DOI Creative Commons
Sheng Yang, Chuan Qin,

Zi-Wei Hu

et al.

Neurobiology of Disease, Journal Year: 2021, Volume and Issue: 152, P. 105290 - 105290

Published: Feb. 6, 2021

In response to various types of environmental and cellular stress, microglia rapidly activate exhibit either pro- or anti-inflammatory phenotypes maintain tissue homeostasis. Activation can result in changes morphology, phagocytosis capacity, secretion cytokines. Furthermore, microglial activation also induces energy demand, which is dependent on the metabolism metabolic substrates including glucose, fatty acids, amino acids. Accumulating evidence demonstrates reprogramming acts as a key driver immune response. For instance, pro-inflammatory states preferentially use glycolysis for production, whereas, cells are mainly powered by oxidative phosphorylation acid oxidation. this review, we summarize recent findings regarding pathways under physiological pathological circumtances. We will then discuss how orchestrate variety central nervous system pathologies. Finally, highlight manipulating reprogram towards beneficial functions, illustrate therapeutic potential inflammation-related neurological diseases.

Language: Английский

Citations

142
Microglial/Macrophage polarization and function in brain injury and repair after stroke DOI Creative Commons

Junxuan Lyu,

Di Xie, Tarun N. Bhatia

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2021, Volume and Issue: 27(5), P. 515 - 527

Published: March 1, 2021

Abstract Stroke is a leading cause of disability and mortality, with limited treatment options. After stroke injury, microglia CNS‐resident macrophages are rapidly activated regulate neuropathological processes to steer the course functional recovery. To accelerate this recovery, can engulf dying cells clear irreparably‐damaged tissues, thereby creating microenvironment that more suitable for formation new neural circuitry. In addition, monocyte‐derived cross compromised blood‐brain barrier infiltrate injured brain. The specific functions myeloid lineage in brain injury repair diverse dependent on phenotypic polarization statuses. However, it remains be determined what degree CNS‐invading occupy different niches from microglia. review, we describe physiological characteristics developing adult We also review (a) activation after stroke, (b) molecular mechanisms control status, (c) contribution pathology versus repair. Finally, summarize current breakthroughs therapeutic strategies calibrate microglia/macrophage responses stroke.

Language: Английский

Citations

129
Phagocytic microglia and macrophages in brain injury and repair DOI Creative Commons
Fang Yu, Yangfan Wang,

Anne R. Stetler

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2022, Volume and Issue: 28(9), P. 1279 - 1293

Published: June 25, 2022

Phagocytosis is the cellular digestion of extracellular particles, such as pathogens and dying cells, a key element in evolution central nervous system (CNS) disorders. Microglia macrophages are professional phagocytes CNS. By clearing toxic debris reshaping matrix, microglia/macrophages help pilot brain repair functional recovery process. However, CNS resident invading immune cells can also magnify tissue damage by igniting runaway inflammation phagocytosing stressed-but viable-neurons.

Language: Английский

Citations

110