Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate

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

Published: April 4, 2022

Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the contributes pathogenesis PSCI.83 patients were recruited and their function measured by Montreal Cognitive Assessment (MoCA) scores 3 months after onset. peripheral inflammatory factor levels compositions analyzed. Fecal transplantation from mice was performed examine causal relationship between PSCI. evaluated Morris water maze test.34 49 classified as non-PSCI, respectively. Compared with non-PSCI patients, showed significantly higher Enterobacteriaceae, lipopolysaccharide (LPS) inflammation markers. Consistently, received (PSCI mice) presented a level intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) cytokines, lower fecal butyrate, severer intestine destruction than nPSCI (nPSCI mice). In addition, observed exacerbations blood-brain barrier (BBB) integrity, microglial activation, neuronal apoptosis CA1 region hippocampus, Aβ deposition thalamus comparison mice. Intraperitoneal injection LPS caused similar pathology those seen Supplementation sodium butyrate (NaB) via drinking rescued these detrimental changes mice.Our data indicate cause-effect for first time, likely mediated inflammation-regulating metabolites including butyrate.

Language: Английский

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Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 13101 - 13101

Published: Dec. 3, 2021

Ischaemic stroke involves the rapid onset of focal neurological dysfunction, most commonly due to an arterial blockage in a specific region brain. Stroke is leading cause death and common disability, with over 17 million people worldwide suffering from each year. It now well-documented that neuroinflammation immune mediators play key role acute long-term neuronal tissue damage healing, not only infarct core but also distal regions. Importantly, these regions, termed sites secondary neurodegeneration (SND), spikes may be seen sometime after initial onset, prior presence within However, it acknowledge that, despite mounting information describing following ischaemic stroke, exact mechanisms whereby inflammatory cells their drive stroke-induced are still fully understood. As result, current anti-inflammatory treatments have failed show efficacy clinical trials. In this review we discuss complexities post-stroke neuroinflammation, specifically how affects outcome acutely, chronically, SND. We then previously assessed therapies, particular focus on anti-inflammatories repurposed target SND-associated neuroinflammation.

Language: Английский

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Brain repair mechanisms after cell therapy for stroke

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3286 - 3305

Published: June 25, 2024

Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, underlying mechanisms by which they promote remain unclear. Here, we briefly review endogenous ischaemic stroke then focus on how different stem progenitor sources can repair. Specifically, examine transplanted grafts contribute to improved functional recovery either through direct replacement or stimulating pathways. Additionally, discuss recently implemented refinement methods, such as preconditioning, microcarriers, genetic safety switches universal (immune evasive) transplants, well therapeutic potential these pharmacologic manipulations further enhance efficacy therapies. By gaining a deeper understanding post-ischaemic mechanisms, prospective trials may be refined advance post-stroke therapy clinic.

Language: Английский

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Neuronal Loss after Stroke Due to Microglial Phagocytosis of Stressed Neurons

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(24), P. 13442 - 13442

Published: Dec. 14, 2021

After stroke, there is a rapid necrosis of all cells in the infarct, followed by delayed loss neurons both brain areas surrounding known as 'selective neuronal loss', and remote from, but connected to, 'secondary neurodegeneration'. Here we review evidence indicating that this after stroke mediated microglial phagocytosis stressed neurons. are ongoing ischemia, excitotoxicity and/or inflammation to: (i) release "find-me" signals such ATP, (ii) expose "eat-me" phosphatidylserine, (iii) bind to opsonins, complement components C1q C3b, inducing microglia phagocytose Blocking these factors on neurons, or their phagocytic receptors microglia, can prevent behavioral deficits rodent models ischemic stroke. Phagocytic may be attractive treatment targets due

Language: Английский

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Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 43(7), P. 1060 - 1076

Published: Feb. 9, 2023

Despite progress in reperfusion therapy, functional recovery remains suboptimal many stroke patients, with oxidative stress, inflammation, dysbiosis, and secondary neurodegeneration constituting the major hurdles to recovery. The essential trace element selenium is emerging as a promising therapeutic agent for stroke. However, although several rodent studies have shown that can protect against cell loss following cerebral ischemia, no study has yet examined whether enhance long-term Moreover, published typically reported single mechanism of action underlying selenium-mediated we propose more likely multifaceted actions. Here, show selenomethionine confers potent neuroprotective effect canonical filament-induced transient middle artery occlusion (tMCAO) mouse model. Post-tMCAO treatment significantly reduces infarct volume, ferroptosis enhances post-tMCAO motor performance acute phase after analysis gut microbiota reveals reverses stroke-induced dysbiosis. Longer-term supplementation activates intrinsic mechanisms, prevents neurodegeneration, alleviates systemic diminishes microbe-derived circulating trimethylamine N-oxide. These findings demonstrate even ischemia effects, highlighting its clinical potential.

Language: Английский

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Targeting foam cell formation to improve recovery from ischemic stroke

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 181, P. 106130 - 106130

Published: April 15, 2023

Inflammation is a crucial part of the healing process after an ischemic stroke and required to restore tissue homeostasis. However, inflammatory response also worsens neurodegeneration creates environment that unfavorable regeneration for several months, thereby postponing recovery. In animal models, inflammation can contribute development delayed cognitive deficits. Myeloid cells take on foamy appearance are one most prominent immune cell types within chronic infarcts. Emerging evidence indicates they form as result mechanisms myelin lipid clearance becoming overwhelmed, key driver stroke. Therefore, targeting accumulation in foam may be promising strategy improving The aim this review provide overview current knowledge regarding formation brain weeks months following identify targets amenable therapeutic intervention.

Language: Английский

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Is Cerebral Amyloid-β Deposition Related to Post-stroke Cognitive Impairment?

Translational Stroke Research, Journal Year: 2021, Volume and Issue: 12(6), P. 946 - 957

Published: June 30, 2021

Language: Английский

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Unravelling the nexus of stroke and dementia: Deciphering the role of secondary neurodegeneration in orchestrating cognitive decline

Neuroprotection/Neuroprotection (Chichester, England. Print), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Stroke is the leading cause of acquired disability. The development acute ischemic stroke treatments, such as mechanical thrombectomy and tissue plasminogen activator, has resulted in more patients surviving initial insult. However, long‐term complications, post‐stroke cognitive impairment (PSCI) dementia (PSD), are at an all‐time high. Notably, 80% survivors suffer from impairment, a history doubles patient's lifetime risk developing dementia. A combination greater life expectancy, increase number strokes young individuals, improved survival have inherently increased years living post‐stroke, highlighting critical need to understand effects stroke, including how pathological changes brain might give rise functional behavioral survivors. Even with this PSCI PSD survivors, understanding itself develops into these conditions remains incomplete. Recently, secondary neurodegeneration (SND) following been linked PSD. SND degeneration regions outside original site. Degeneration sites thought arise due diaschisis infarct core; however, observation pathology multiple without direct connectivity suggests that likely complex. Moreover, hallmarks dementia, deposition neurodegenerative proteins iron, cell death, inflammation blood–brain barrier alterations, all found thalamus, hippocampus, basal ganglia, amygdala prefrontal cortex stroke. Hence, review, we present current context outline remote anatomical molecular may drive conditions.

Language: Английский

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Impaired glymphatic system is associated with secondary neuronal injury in the thalamus following cerebral cortical infarction

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111330 - 111330

Published: April 1, 2025

Language: Английский

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Novel Perivascular Macrophage Mechanism to Promote Glymphatic Aβ Clearance After Stroke

Stroke, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

BACKGROUND: Parenchymal border macrophages (PBMs) reside at the interface between central nervous system and periphery. They are known to mediate accessibility of substances brain. However, no one has examined their role in poststroke Aβ (amyloid-β) clearance. METHODS: Permanent focal cerebral ischemia was induced 8- 10-week-old C57/Bl6 male mice by distal middle artery occlusion. The clodronate liposomes were administered into spinal fluid 7 days before stroke deplete PBM population. Sensorimotor cognitive functions, glymphatic system, accumulation assessed for up 34 after stroke. RESULTS: accumulated along brain blood vessels both ipsilateral contralateral hemispheres. When PBMs depleted, drainage markedly reduced, this accompanied deterioration function, highlighting a critical disposal. A possible mechanism relates MANF (mesencephalic astrocyte-derived neurotrophic factor). derived from suppressed astrocytic stress maintained when supplemented fluid. In chronic phase stroke, production downregulated, consequently, impairments exacerbated, which led ongoing decline. CONCLUSIONS: summary, supplementation not only mitigates adverse impacts depletion but also exerts therapeutic effects that improve function. We thus propose represents promising strategy prevent impairment.

Language: Английский

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