Synaptic Plasticity As A Mechanistic Basis For Cognitive Rehabilitation After Stroke: A Systematic Review

Abstract

Stroke is one of the leading global causes of long-term disability, with nearly two-thirds of survivors experiencing persistent cognitive impairments such as memory dysfunction, executive deficits, and reduced attentional capacity. These cognitive sequelae significantly compromise functional independence and quality of life. In recent years, synaptic plasticity—the dynamic ability of synapses to undergo functional and structural modifications—has emerged as a critical mechanism underlying cognitive recovery. This systematic review synthesizes evidence from preclinical and clinical studies published between 2000 and 2025, examining the role of synaptic plasticity in post-stroke cognitive rehabilitation. We evaluate key neurobiological processes, including long-term potentiation (LTP), long-term depression (LTD), dendritic spine remodeling, and neurotrophic factor signaling, in reshaping neural circuits after stroke. Furthermore, we analyze how rehabilitation interventions such as cognitive training, aerobic exercise, enriched environments, pharmacological agents, and non-invasive brain stimulation modulate synaptic plasticity and contribute to improved cognitive outcomes. Findings suggest that interventions enhancing LTP and dendritic complexity through neurotrophic modulation are strongly associated with functional recovery. However, translation of animal findings to human clinical contexts remains limited by methodological heterogeneity, small sample sizes, and underutilization of synaptic biomarkers. The review underscores the necessity of longitudinal, multimodal, and precision-based approaches that integrate behavioral rehabilitation with neuroplasticity-targeting strategies. By bridging mechanistic insights with therapeutic interventions, this review highlights the potential of harnessing synaptic plasticity to optimize cognitive rehabilitation post-stroke and proposes directions for future research aimed at strengthening clinical evidence.