Unraveling brain diseases: The promise of brain-on-a-chip models

Journal of Neuroscience Methods, Journal Year: 2024, Volume and Issue: 405, P. 110105 - 110105

Published: March 7, 2024

Brain disorders, encompassing a wide spectrum of neurological and psychiatric conditions, present formidable challenge in modern medicine. Despite decades research, the intricate complexity human brain still eludes comprehensive understanding, impeding development effective treatments. Recent advancements microfluidics tissue engineering have led to innovative platforms known as "Brain-on-a-Chip" (BoC) i.e., advanced vitro systems that aim replicate microenvironment with highest possible fidelity. This technology offers promising test-bed for studying disorders at cellular network levels, providing insights into disease mechanisms, drug screening, and, perspective, personalized therapeutic strategies. In this review, we provide an overview BoC models developed over years model understand onset progression some most severe terms incidence debilitation (stroke, Parkinson's, Alzheimer's, epilepsy). We also report cutting-edge approaches whose effects were evaluated by means these technologies. Finally, discuss potential challenges, future perspectives models.

Language: Английский

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Current evidence of synaptic dysfunction after stroke: Cellular and molecular mechanisms

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(5)

Published: May 1, 2024

Stroke is an acute cerebrovascular disease in which brain tissue damaged due to sudden obstruction of blood flow the or rupture vessels brain, can prompt ischemic hemorrhagic stroke. After stroke onset, ischemia, hypoxia, infiltration components into parenchyma, and lysed cell fragments, among other factors, invariably increase blood-brain barrier (BBB) permeability, inflammatory response, edema. These changes lead neuronal death synaptic dysfunction, latter poses a significant challenge treatment.

Language: Английский

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Metabolic reprogramming and astrocytes polarization following ischemic stroke

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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The role of astrocyte metabolic reprogramming in ischemic stroke (Review)

International Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: 55(3)

Published: Jan. 21, 2025

Ischemic stroke, a leading cause of disability and mortality worldwide, is characterized by the sudden loss blood flow in specific area brain. Intravenous thrombolysis with recombinant tissue plasminogen activator only approved pharmacological treatment for acute ischemic stroke; however, aforementioned has significant clinical limitations, thus there an urgent need development novel mechanisms therapeutic strategies stroke. Astrocytes, abundant versatile cells central nervous system, offer crucial support to neurons nutritionally, structurally physically. They also contribute blood‑brain barrier formation regulate neuronal extracellular ion concentrations. Accumulated evidence revealed involvement astrocytes regulation host neurotransmitter metabolism, immune response repair, different metabolic characteristics can process suggesting that targeted astrocyte reprogramming may prognosis In present review, current understanding multifaceted along its regulatory factors pathways, as well promote polarization balance, which hold promise immunometabolism‑targeted therapies were summarized.

Language: Английский

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Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9381 - 9381

Published: Aug. 19, 2022

Stroke is one of the leading causes death and disability in world, which ischemia accounts for majority. There growing evidence changes synaptic connections neural network functions brain stroke patients. Currently, studies on these neurobiological alterations mainly focus principle glutamate excitotoxicity, corresponding neuroprotective strategies are limited to blocking overactivation ionic receptors. Nevertheless, it disappointing that treatments often fail because unspecificity serious side effects tested drugs clinical trials. Thus, prevention treatment stroke, finding developing new targets intervention still goal research this field. In review, we whole processes glutamatergic transmission highlight pathological underlying each link help develop potential therapeutic ischemic damage. These include: (1) controlling or extra-synaptic release glutamate, (2) selectively action receptor NMDAR subunit, (3) increasing metabolism, reuptake blood, (4) regulating system by GABA receptors microbiota-gut-brain axis. Based latest findings, expected promote a substantial understanding complex signal transduction mechanism, thereby providing excellent neuroprotection direction human (IS).

Language: Английский

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Post-Stroke Neuropsychiatric Complications: Types, Pathogenesis, and Therapeutic Intervention

Aging and Disease, Journal Year: 2023, Volume and Issue: 14(6), P. 2127 - 2127

Published: Jan. 1, 2023

Almost all stroke survivors suffer physical disabilities and neuropsychiatric disturbances, which can be briefly divided into post-stroke neurological diseases psychiatric disorders. The former type mainly includes pain, epilepsy, dementia while the latter one depression, anxiety, apathy fatigue. Multiple risk factors are related to these complications, such as age, gender, lifestyle, type, medication, lesion location, comorbidities. Recent studies have revealed several critical mechanisms underlying namely inflammatory response, dysregulation of hypothalamic pituitary adrenal axis, cholinergic dysfunction, reduced level 5-hydroxytryptamine, glutamate-mediated excitotoxicity mitochondrial dysfunction. Moreover, clinical efforts successfully given birth many practical pharmaceutic strategies, anti-inflammatory medications, acetylcholinesterase inhibitors, selective serotonin reuptake well diverse rehabilitative modalities help patients physically mentally. However, efficacy interventions is still under debate. Further investigations from both basic perspectives, urgent for development effective treatment strategies.

Language: Английский

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“No-reflow” phenomenon in acute ischemic stroke

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 44(1), P. 19 - 37

Published: Oct. 19, 2023

Acute ischemic stroke (AIS) afflicts millions of individuals worldwide. Despite the advancements in thrombolysis and thrombectomy facilitating proximal large artery recanalization, resultant distal hypoperfusion, referred to “no-reflow” phenomenon, often impedes neurological function restoration patients. Over half a century scientific inquiry has validated existence cerebral both animal models human subjects. Furthermore, correlation between adverse clinical outcomes underscores necessity address this phenomenon as pivotal strategy for enhancing AIS prognoses. The underlying mechanisms are multifaceted, encompassing formation microemboli, microvascular compression contraction. Moreover, myriad complex warrant further investigation. Insights gleaned from mechanistic exploration have prompted treatment, including microthrombosis therapy, which demonstrated efficacy improving patient stagnation current diagnostic methods imposes limitations on timely application combined therapy post-recanalization. This narrative review will traverse historical journey delve into its underpinnings AIS, elucidate potential therapeutic strategies. Our aim is equip readers with swift comprehension highlight critical points future research endeavors.

Language: Английский

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Assessing the causal effect of genetically predicted metabolites and metabolic pathways on stroke

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 17, 2023

Abstract Background Stroke is a common neurological disorder that disproportionately affects middle-aged and elderly individuals, leading to significant disability mortality. Recently, human blood metabolites have been discovered be useful in unraveling the underlying biological mechanisms of disorders. Therefore, we aimed evaluate causal relationship between susceptibility stroke. Methods Summary data from genome-wide association studies (GWASs) serum stroke its subtypes were obtained separately. A total 486 used as exposure. Simultaneously, 11 different phenotypes set outcomes, including any (AS), ischemic (AIS), large artery (LAS), cardioembolic (CES), small vessel (SVS), lacunar (LS), white matter hyperintensities (WMH), intracerebral hemorrhage (ICH), subarachnoid (SAH), transient attack (TIA), brain microbleeds (BMB). two‐sample Mendelian randomization (MR) study was conducted investigate effects on subtypes. The inverse variance-weighted MR analyses estimates, accompanied by series sensitivity robustness results. Furthermore, reverse analysis assess potential for causation. Additionally, metabolic pathway performed using web-based MetOrigin . Results After correcting false discovery rate (FDR), results revealed remarkable causative associations with 25 metabolites. Further confirmed only four involving three specific passed all tests, namely ADpSGEGDFXAEGGGVR* AS (OR: 1.599, 95% CI 1.283–1.993, p = 2.92 × 10 −5 ) AIS 1.776, 1.380–2.285, 8.05 −6 ), 1-linoleoylglycerophosph-oethanolamine* LAS 0.198, 0.091–0.428, 3.92 gamma-glutamylmethionine* SAH 3.251, 1.876–5.635, 2.66 thereby demonstrating high degree stability. Moreover, eight seven other both tests considered robust. result one metabolite (glutamate LAS) non-robust. As remaining metabolites, speculate they may potentially possess relationships. Notably, no emerged analysis. after FDR correction, identified 40 pathways across phenotypes. Conclusions their associated are promising circulating biomarkers, holding application screening preventive strategies within clinical settings.

Language: Английский

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A New Perspective in the Treatment of Ischemic Stroke: Ferroptosis

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(4), P. 815 - 833

Published: Jan. 3, 2024

Language: Английский

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Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 22, 2024

Abstract Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window associated risks underscore necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as promising therapeutic approach due to ability modulate post-stroke microenvironment facilitate neuroprotection neurorestoration. This review synthesizes current research on potential stem EVs AIS, focusing origin, biogenesis, mechanisms action, strategies enhancing targeting capacity efficacy. Additionally, we explore innovative combination therapies discuss both challenges prospects EV-based treatments. Our findings reveal that exhibit diverse effects such promoting neuronal survival, diminishing neuroinflammation, protecting blood-brain barrier, angiogenesis neurogenesis. Various strategies, including modifications cargo modifications, been developed improve efficacy EVs. Combining other treatments, therapy, cell transplantation, nanomedicine, gut microbiome modulation, holds great promise improving outcomes. However, heterogeneity need standardized protocols EV production quality control remain be addressed. represent avenue offering address limitations Further needed optimize translate benefits clinical practice, an emphasis ensuring safety, overcoming regulatory hurdles, specificity delivery target tissues. Graphical

Language: Английский

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