1,721,048 research outputs found
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
No full textOlder 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
Translatability of life‐extending pharmacological treatments between different species
No full textAbstract Anti‐aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti‐aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti‐aging treatments to human applications presents a considerable challenge. This discrepancy can be attributed to the increasing complexity of biological systems, species‐specific metabolic and genetic differences, and the redundancy of metabolic pathways linked to longevity. Our review focuses on analyzing these challenges, offering insights into the efficacy of anti‐aging mechanisms across species and identifying key barriers to their translation into human treatments. By synthesizing current knowledge and identifying gaps in translatability, this review aims to underscore the importance of advancing these therapies for human benefit. Bridging this gap is essential to assess the potential of such treatments in extending the human healthspan.Funder:
European Commission
https://doi.org/10.13039/501100000780Funder:
Deutsche Forschungsgemeinschaft
https://doi.org/10.13039/50110000165
Ischemic stroke and comorbidities: Impact on recovery and the role of genetics and epigenetics
No full texthttp://dx.doi.org/10.13039/501100013831 Universitatea de Medicină şi Farmacie din Craiovahttp://dx.doi.org/10.13039/501100000780 European Commissio
Vascular Aging and Multi-Omic Regulation in Ischemic Stroke: Toward Precision Neurorepair
No full textOpportunities and Limitations of Vascular Risk Factor Models in Studying Plasticity-Promoting and Restorative Ischemic Stroke Therapies
No full textMajor efforts are currently made promoting neuronal plasticity and brain remodeling in the postacute stroke phase. Experimental studies evaluating new stroke therapies are mostly performed in rodents, which compared to humans exhibit a short lifespan. These studies widely employ young, otherwise healthy, rodents that lack the vascular risk factors and comorbidities of stroke patients. These risk factors compromise postischemic neurological recovery and brain plasticity and in several contexts reduce the brain responsiveness to recovery-inducing plasticity-promoting treatments. By examining risk factor models, which have hitherto been used for studying experimentally induced ischemic stroke, this review outlines the possibilities and limitations of risk factor models in the evaluation of plasticity-promoting and restorative stroke treatments
Animal models of ischemic stroke and their impact on drug discovery
No full textIntroduction: Representing the leading cause of long-term disability, ischemic stroke urgently needs further research and drug development. This review summarizes current animal models of ischemic stroke that can be used for drug discovery.
Areas covered: Several reproducible models of permanent and transient focal cerebral ischemia have been established in a variety of animal species including rats and mice, in which a brain-supplying artery, often the middle cerebral artery, is occluded by mechanical devices including sutures, clips and hooks, pharmacological agents or delivery of blot clots. The authors review existing literature about these models, outlining their utility for evaluating acute and post-acute stroke treatments. Since stroke is an age-related disease that strongly affects humans with vascular risk factors and co-morbidities, the authors give focus to strategies replicating risk factors in ischemic stroke models. Furthermore, the authors present models of spontaneous stroke.
Expert opinion: It is important that animal models mimic clinical conditions in a reliable and clinically relevant way, so here, they should replicate the pathophysiology of human stroke, stroke-associated risk factors and doses, times and modes of drug treatment. We propose that risk factor models should more widely be used in early drug discovery, if possible already during the identification of treatment targets.No Full Tex
Pharmacological and stem cell therapy of stroke in animal models: Do they accurately reflect the response of humans?
No full texthttp://dx.doi.org/10.13039/501100013831 Universitatea de Medicina si Farmacie din Craiov
Targeting the Biology of Aging in Cerebrovascular Disease: Inflammation, Metabolism, Senescence, and Regeneration
No full textAging is the strongest independent risk factor for cerebrovascular diseases, profoundly influencing vascular structure, immune responses, and regenerative capacity of the brain. Traditional therapeutic strategies, largely developed in younger populations, often show reduced efficacy and increased risk in elderly patients, underscoring the need for age-adapted interventions. Advances in the understanding of cerebrovascular aging have revealed key mechanisms such as vascular senescence, chronic low-grade inflammation, blood–brain barrier dysfunction, mitochondrial impairment, and circadian dysregulation as central drivers of disease progression and poor recovery. This narrative review summarizes emerging therapeutic strategies targeting the molecular and cellular hallmarks of aging-related cerebrovascular disease. These include immunomodulatory and anti-inflammatory approaches, senescence-targeted therapies, stem cell and extracellular vesicle-based regenerative strategies, RNA-based interventions, and metabolic and mitochondrial modulation. Particular emphasis is placed on therapies aimed at restoring neurovascular unit integrity and promoting brain repair in the aged microenvironment. Additionally, this review highlights the growing role of chronobiology and precision medicine, integrating biomarkers and multi-omics approaches to tailor treatments for elderly patients. Collectively, these emerging therapies represent a paradigm shift from symptom-oriented management toward mechanism-based and personalized interventions. Addressing age-specific pathophysiology will be critical for improving outcomes in cerebrovascular diseases in the aging population and for translating experimental advances into effective clinical therapies.European Union, under the PNRR Programme “Targeting Macrophages/Monocytes in the Aged Ischemic Brain by Pharmacological, Genetic, and Cell-Based Tools,”UEFISCDI Projec
Correction: Immune genes involved in synaptic plasticity during early postnatal brain development contribute to post-stroke damage in the aging male rat brain
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