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与年龄相关的神经可塑性下降及其对脑缺血动物模型中风后恢复的影响:细胞外囊泡的治疗作用。

The age-associated decline in neuroplasticity and its implications for post-stroke recovery in animal models of cerebral ischemia: The therapeutic role of extracellular vesicles.

作者信息

Popa-Wagner Aurel, Hermann Dirk M, Doeppner Thorsten R, Surugiu Roxana, Pirscoveanu Denisa Fv

机构信息

Chair of Vascular Neurology and Dementia, Department of Neurology, University Hospital Essen, Essen, Germany.

Experimental Research Center for Normal and Pathological Aging, University of Medicine and Pharmacy Craiova, Craiova, Romania.

出版信息

J Cereb Blood Flow Metab. 2025 Aug 6:271678X251365020. doi: 10.1177/0271678X251365020.


DOI:10.1177/0271678X251365020
PMID:40770923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12331653/
Abstract

Older individuals are typically more susceptible to stroke, and age-related differences in brain plasticity significantly affect recovery and treatment responses following cerebral ischemia and traumatic brain injury. Extracellular vesicles (EVs) have emerged as promising diagnostic and therapeutic tools due to their role in intercellular communication and ability to cross the blood-brain barrier. While EVs hold potential in promoting brain repair, their efficacy is influenced by donor age-those derived from young stem cells exhibit more regenerative profiles, whereas aged donor EVs may carry senescence-related signals that impede recovery. Emerging therapies, including senolytics, exosome-based approaches, and immune modulation, aim to enhance post-stroke repair, yet a substantial translational gap persists, especially in adapting these strategies to the aged brain. Differences in immune responses, neurovascular integrity, and repair mechanisms between young and aged individuals further complicate therapeutic development. Incorporating aged animal models in preclinical research is thus essential for ensuring the relevance and safety of interventions in elderly patients. These findings underscore the need for age-tailored strategies that reflect the unique biological landscape of aging, paving the way for more effective treatments for stroke and related neurological conditions in older adults.

摘要

老年人通常更容易患中风,大脑可塑性的年龄相关差异会显著影响脑缺血和创伤性脑损伤后的恢复及治疗反应。细胞外囊泡(EVs)因其在细胞间通讯中的作用以及穿越血脑屏障的能力,已成为有前景的诊断和治疗工具。虽然细胞外囊泡在促进脑修复方面具有潜力,但其功效受供体年龄影响——源自年轻干细胞的细胞外囊泡表现出更多的再生特性,而老年供体细胞外囊泡可能携带阻碍恢复的衰老相关信号。包括衰老细胞溶解剂、基于外泌体的方法和免疫调节在内的新兴疗法旨在增强中风后的修复,但仍存在很大的转化差距,尤其是在将这些策略应用于老年大脑方面。年轻人和老年人之间免疫反应、神经血管完整性和修复机制的差异使治疗开发更加复杂。因此,在临床前研究中纳入老年动物模型对于确保干预措施对老年患者的相关性和安全性至关重要。这些发现强调了需要制定适合年龄的策略,以反映衰老独特的生物学特征,为更有效地治疗老年人中风及相关神经疾病铺平道路。

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The age-associated decline in neuroplasticity and its implications for post-stroke recovery in animal models of cerebral ischemia: The therapeutic role of extracellular vesicles.

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本文引用的文献

[1]
Extracellular Vesicle-Derived miRNAs in Ischemic Stroke: Roles in Neuroprotection, Tissue Regeneration, and Biomarker Potential.

Cell Mol Neurobiol. 2025-3-31

[2]
Extracellular vesicles: new horizons in neurodegeneration.

EBioMedicine. 2025-3

[3]
Research progress on the mechanisms of microglial extracellular vesicles affecting the prognosis of ischemic stroke.

Neurochem Int. 2025-5

[4]
On the road: extracellular vesicles in intercellular communication.

Cell Commun Signal. 2025-2-18

[5]
Immune genes involved in synaptic plasticity during early postnatal brain development contribute to post-stroke damage in the aging male rat brain.

Biogerontology. 2025-2-18

[6]
Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in ischemic stroke: A meta-analysis of preclinical studies.

Brain Res Bull. 2025-2

[7]
Dual role of extracellular vesicles in neurodegenerative diseases.

World J Stem Cells. 2024-12-26

[8]
Astrocyte-neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury.

Exp Mol Med. 2024-12

[9]
The Influence of Circulating Exosomes Derived From Younger and Older Donors on Hypoxia-Inducible Factor 1 Alpha Gene Expression and P21 Protein in Cord Blood Hematopoietic Stem Cells.

J Hematol. 2024-10

[10]
Aging, brain plasticity, and motor learning.

Ageing Res Rev. 2024-12

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