Astrocyte-neuron interactions as modulators of neural plasticity in stroke recovery: implications for rehabilitation strategies

Stroke remains a leading cause of global mortality and disability, necessitating innovative rehabilitation strategies to enhance recovery. Interactions between astrocytes and neurons modulate neural plasticity. This review synthesizes current evidence on the role of astrocytes in stroke recovery, focusing on their contributions to neural plasticity through neurotransmitter homeostasis, gliotransmission, neurotrophic factor release, metabolic support, modulation of inflammation, and extracellular matrix remodeling. Astrocytes regulate synaptic function via glutamate uptake and D-serine release, support neuronal survival through brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), and shape the neuroinflammatory response via crosstalk with microglia. While reactive astrocytes form protective glial scars, they also pose barriers to axonal regeneration. We explore astrocyte-targeted therapeutic strategies, including pharmacological interventions (minocycline, celastrol), non-invasive neuromodulation (tDCS, rTMS), stem cell therapy, and cellular reprogramming, highlighting their potential to enhance plasticity and recovery. Challenges such as limited translational models, difficulties isolating astrocyte-specific effects, and methodological constraints in imaging are discussed, alongside future directions involving single-cell transcriptomics to address astrocyte heterogeneity. By elucidating the multifaceted roles of astrocytes, this review highlights their therapeutic potential in stroke rehabilitation and advocates targeted interventions to optimize neuroprotection and circuit rewiring.