Muscle‐Derived Small Extracellular Vesicles Mediate Exercise‐Induced Cognitive Protection in Chronic Cerebral Hypoperfusion

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Abstract Physical exercise protects against cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, the mechanisms through which sends signals from periphery to central nervous system remain incompletely understood. This study demonstrated that promotes secretion of muscle‐derived small extracellular vesicles (sEVs), facilitate interorgan communication between muscle and brain. Systematic delivery sEVs enhances synaptic plasticity alleviated in CCH. Notably, miRNA sequencing reveal miR‐17/20a‐5p as key cargos involved exercise‐induced muscle‐brain crosstalk. Muscle‐derived are also identified primary source swimming‐induced circulating sEVs. Mechanistically, binds DEP‐domain containing mTOR‐interacting protein (DEPTOR) activates mammalian target rapamycin (mTOR) pathway hippocampus. Depletion impairs enhancement function. Moreover, overexpression DEPTOR hippocampus attenuates benefits exercise. Conversely, hippocampus‐specific activation mTOR reverses these effects, highlighting crucial role mediating positive effects Collectively, findings identify myokine with potent on brain, emphasizing therapeutic potential managing impairment.

Язык: Английский

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Unravelling the Brain Resilience Following Stroke: From injury to rewiring of the brain through pathway activation, drug targets, and therapeutic interventions

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102780 - 102780

Опубликована: Май 1, 2025

Язык: Английский

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The activation of AMPK/PGC-1α/GLUT4 signaling pathway through early exercise improves mitochondrial function and mitigates ischemic brain damage

Neuroreport, Год журнала: 2024, Номер 35(10), С. 648 - 656

Опубликована: Май 15, 2024

Mitochondria play a crucial role in maintaining cellular energy supply and serve as source of for repairing nerve damage following stroke. Given that exercise has the potential to enhance metabolism, investigating impact on mitochondrial function provides plausible mechanism stroke treatment. In our study, we established middle cerebral artery occlusion (MCAO) model Sprague–Dawley rats implemented early intervention. Neurological severity scores, beam-walking test score, weight were used evaluate neurological function. The volume infarction was measured by MRI. Nerve cell apoptosis detected TUNEL staining. Mitochondrial morphology structure electron microscopy. assessed using membrane ATP measurements. Western blotting detect protein expression AMPK/PGC-1α/GLUT4. Through above experiments, found improved after MCAO, reduced neuronal apoptosis, promoted recovery We further examined AMPK/PGC-1α/GLUT4 signaling pathway confirmed able increase its expression. Therefore, suggest initiated pathway, restoring augmenting supply. This, turn, effectively both body ischemic

Язык: Английский

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Rehabilitation Training after Spinal Cord Injury Affects Brain Structure and Function: From Mechanisms to Methods

Biomedicines, Год журнала: 2023, Номер 12(1), С. 41 - 41

Опубликована: Дек. 22, 2023

Spinal cord injury (SCI) is a serious neurological insult that disrupts the ascending and descending neural pathways between peripheral nerves brain, leading to not only functional deficits in injured area below level of lesion but also morphological, structural, reorganization brain. These changes introduce new challenges uncertainties into treatment SCI. Rehabilitation training, clinical intervention designed promote recovery after spinal brain injuries, has been reported activation cerebral cortex through multiple physiological mechanisms. In this review, we evaluate potential mechanisms exercise affect structure function, as well rehabilitation training process for Additionally, compare discuss principles, effects, future directions several methods facilitate Understanding regulatory role at supraspinal center great significance clinicians develop SCI strategies optimize plans.

Язык: Английский

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Exosome-based regenerative rehabilitation: A novel ice breaker for neurological disorders

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 169, С. 115920 - 115920

Опубликована: Ноя. 22, 2023

Neurological disorders affect a large population, often leading to different levels of disability and resulting in decreased quality life. Due the limited recovery obtained from surgical procedures other medical approaches, number patients with prolonged dysfunction receive neurorehabilitation protocols improve their neural plasticity regeneration. However, poor regeneration ability cannot effectively rebuild tissue integrity functional networks; consequently, prognoses remain undetermined. To increase chances for neurological disorders, regenerative rehabilitation was introduced combined medicine repair damage create an optimized biophysical microenvironment potential. With deepening exosome research, increasing studies have found that systemic therapeutic effects approaches are mediated by exosomes released physically stimulated cells, which provides new insight into rehabilitative mechanisms. Meanwhile, therapy also serves as alternative cell-free is applied partnership formulates exosome-based rehabilitation. In this study, we review current state exosome-associated neurorehabilitation. On one hand, focus on presenting varied mediating specific pathologies; discuss diverse combinations therapies field rehabilitation, aiming awareness research applications disorders.

Язык: Английский

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Tanshinone IIA Regulates Synaptic Plasticity in Mg2+-Free-Induced Epileptic Hippocampal Neurons via the PI3K/Akt Signaling Pathway

Journal of Integrative Neuroscience, Год журнала: 2024, Номер 23(3)

Опубликована: Март 19, 2024

Background: Tanshinone IIA (TSIIA) is an element of the effective ingredients Salvia miltiorrhiza Bunge (Labiatae), exhibits a significant therapeutic effect in brain neuroprotection. The focus this study was examination synaptic plasticity Mg2+-free-induced epileptic hippocampus neurons and how TSIIA protects against it. Methods: purity primary hippocampal extracted from Sprague Dawley rats assessed within 24 hours by microtubule-associated protein (MAP2) immunofluorescence staining. A neuron model for spontaneous recurrent epileptiform discharge developed, five experimental groups were then randomized: blank (Blank), (Model), (TSIIA, 20 µM), LY294002 (LY294002, 25 TSIIA+LY294002 (TSIIA+LY294002, µM+25 µM). FIJI software used to examine variations neurite complexity, total length neurons, number dendrites density dendritic spines. Developmental regulation (Drebrin) brain-derived neurotrophic factor (BDNF) expression evaluated using staining relative phospho-protein kinase B (p-Akt)/Akt, BDNF, synaptophysin (SYN) postsynaptic 95 (PSD-95) determined Western blot. Results: In contrast group, drastically reduced damage caused epilepsy (p < 0.05). group showed increase PSD-95, SYN, p-Akt/Akt 0.01). Conclusions: reducing harm induced persistent status epilepticus, with possible mechanism being phosphatidylinositol 3-kinase 56 (PI3K)/Akt signaling pathway.

Язык: Английский

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Recovery after human bone marrow mesenchymal stem cells (hBM-MSCs)-derived extracellular vesicles (EVs) treatment in post-MCAO rats requires repeated handling

PLoS ONE, Год журнала: 2024, Номер 19(10), С. e0312298 - e0312298

Опубликована: Окт. 21, 2024

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising restoring brain damage and models. Additionally, non-invasive intranasal route allows EVs reach target specific regions. Yet unclear how handling might enhance recovery or influence other therapies such as after We used transient middle cerebral artery occlusion (MCAO) model rats assess alone, form behavioral tests, combination with an treatment restored neurological damage. Handled were exposed a battery including modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, cylinder together Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, 28 days post-stroke (dps). MCAO also multidose single dose EVs. Non-handled evaluated by mNSS MRI 28, 56 dps treated Our results showed animals necessary for work tested frequency, cumulative further recovered during handling. These show importance rehabilitation treatments EVs, highlight extensive testing functional

Язык: Английский

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Effects of a 12-week, seated, virtual, home-based tele-exercise programme compared with a prerecorded video-based exercise programme in people with chronic neurological impairments: protocol for a randomised controlled trial

BMJ Open, Год журнала: 2023, Номер 13(1), С. e065032 - e065032

Опубликована: Янв. 1, 2023

Introduction Exercise is vital to staying well and preventing secondary complications in people with chronic neurological impairments (CNI). Appropriate exercise often inaccessible this population. The purpose of the study investigate effects a seated, virtual programme on heart rate, recovery, fatigue, pain, motivation, enjoyment quality life CNI. Methods analysis Individuals CNI will be screened for eligibility, 60 participants randomised 1:1 into either live or prerecorded group. There no geographical limitation where reside, since participation virtual. coordinated by one site White Plains, New York, USA. group an instructor via Zoom while at their chosen time using videos, 3×/week 12 weeks. Primary outcome measures: change rate during exercise/recovery. Secondary level pain exertion, physical well-being, activity, motivation life. Outcomes assessed baseline, midpoint, end 1-month poststudy. Adverse events, medication changes activity tracked throughout. Within-group between-group comparisons performed covariance regression. Ethics dissemination BRANY IRB approval: 22 September 2020, protocol #20-08-388-512. All provide written informed consent. Results disseminated through presentations, publications ClinicalTrials.gov. Trial registration number NCT04564495 .

Язык: Английский

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Exosomes as biomarkers and therapeutic measures for ischemic stroke

European Journal of Pharmacology, Год журнала: 2022, Номер 939, С. 175477 - 175477

Опубликована: Дек. 18, 2022

Язык: Английский

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Early exercise intervention promotes myelin repair in the brains of ischemic rats by inhibiting the MEK/ERK pathway

Translational Neuroscience, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 1, 2024

Our previous studies have shown that early exercise intervention after stroke increases neural activity and synaptic plasticity promotes the recovery of nerve fiber bundle integrity in brain. However, effect on repair myelin brain related mechanism are still unclear. In this study, we randomly divided rats into three groups. Before 28 days intervention, body weight, function, infarct size, white matter integrity, structure function were observed by measuring analysis modified neurological severity score, CatWalk gait analysis, MRI, luxol fast blue staining, immunofluorescence, transmission electron microscopy. Changes expression proteins MEK/ERK pathway assessed. The results showed resulted recovery, decreased volume increased coverage area, basic protein (MBP) fluorescence intensity expression, thickness. Furthermore, level MBP was significantly while levels p-MEK1/2 p-ERK1/2 reduced. cell higher oxygen glucose deprivation administration group.In summary, can promote inhibiting signaling pathway.

Язык: Английский

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