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

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.

Keywords: Aging; behavioural recovery; extracellular vesicles; mesenchymal stem cell; stroke.

Figure 1.

Hypothetical modulation of motor neuron activity via astrocyte-derived extracellular vesicles (EVs).

Figure 2.

Extracellular vesicle (EV)-based stroke therapy: Intravenously administered extracellular vesicles derived from mesenchymal stem cells promote angiogenesis, neurogenesis, and behavioral recovery, likely through a bystander effect.