Abstract

A stroke is a medical emergency characterized by the sudden interruption of blood flow to the brain, leading to cell death from oxygen deprivation. As a leading cause of mortality and long-term disability worldwide, strokes present a growing socioeconomic challenge, exacerbated by demographic shifts and an increasing incidence in younger populations. Analyzing post-stroke conditions is essential for predicting recovery trajectories and guiding personalized treatments. The process is crucial for mitigating long-term cognitive deficits and improving the quality of life for stroke survivors and their families. Epigenetic mechanisms are emerging as key influencers, with four significant modulators—miRNAs, lncRNAs, DNA methylation, and histone modifications—being identified as central to modulating neuronal repair and regeneration. However, this is a lack of knowledge as to how major epigenetic signatures affect post-stroke recovery. The paper systematically reviews the capacity of miRNAs to fine-tune neuroprotective responses and the broader regulatory functions of lncRNAs. Additionally, we examine how shifts in DNA methylation patterns and histone modifications correlate with stroke outcomes, presenting a case for precise epigenetic therapies. In this review, we highlight that these modulators offer promising therapeutic targets for enhancing recovery and provide novel insights into stroke pathology and treatment. We also offer a comparative analysis of the four modulators and present the challenges and future perspectives for each one. The review sets forth a trajectory for future research, underscoring the development of novel epigenetic-based therapeutics as a groundbreaking approach to enhance post-stroke neurorehabilitation and improve patient prognoses.

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