Unravelling the brain resilience following stroke: From injury to rewiring of the brain through pathway activation, drug targets, and therapeutic interventions.
Journal:
Ageing research reviews
Published Date:
Jul 1, 2025
Abstract
Synaptic plasticity is a neuron's intrinsic ability to make new connections throughout life. The morphology and function of synapses are highly susceptible to any pathological condition. Ischemic stroke is a cerebrovascular event that affects various brain regions, resulting in the loss of neural networks. Stroke can alter both structural and functional plasticity of synapses, leading to long-term functional disability. Upon ischemic insult, numerous glutamate-mediated synaptic destruction pathways and glial-mediated phagocytic activity are triggered, resulting in excessive synapse loss, altering synaptic plasticity. The conventional stroke therapies to improve synaptic plasticity are still limited and ineffectual, leading to sub-optimal recovery in patients. Therefore, promoting synaptic plasticity to ameliorate sensory-motor function may be a promising strategy for long-term recovery in stroke patients. Here, we review the involvement of different molecular pathways of glutamate and glia-mediated synapse loss, current pharmacological targets, and the emerging novel approaches to improve synaptic plasticity and sensory-motor impairment post-stroke.