This Research Topic aims to promote the discovery of biomarkers and preventative treatments for stroke by leveraging a range of experimental research models to dissect the pathophysiological mechanisms underlying blood–brain barrier (BBB) breakdown. Central to this process are oxidative stress and mitochondrial dysfunction, which are now recognized as key drivers of BBB disruption and stroke pathology.

Stroke is a leading cause of death and disability worldwide, with a complex pathophysiology involving molecular, cellular, and systemic factors. The heterogeneity of stroke etiologies—including large-artery atherosclerosis, cardioembolism, cerebral microbleeds, and small-vessel disease with chronic inflammation—means that a one-size-fits-all approach is often inadequate. Translational research models are critical to capturing the multifaceted nature of stroke, providing insight into how key pathogenic factors lead to brain injury. Ultimately, these models bridge bench-to-bedside, enabling discovery of biomarkers and development of targeted interventions for both prevention and acute management (e.g., differential diagnosis, patient stratification).

Interdisciplinary research that connects basic molecular science with clinical practice is essential to transform mechanistic insights into improved diagnostics and risk assessment. We welcome submissions from all areas of translational and clinical neuroscience, including in vitro and in vivo stroke models, as well as computational–experimental systems that mimic BBB dysfunction. Approaches that particularly effective in dissecting oxidative pathways, mitochondrial damage, and their downstream effects on the neurovascular unit and BBB are of particular interest. Biomarker discovery via high-throughput omics (e.g., transcriptomics, metabolomics) and in silico studies is particularly relevant.

We are especially interested in the following areas:

o Neurovascular Unit (NVU) Injury: We invite studies elucidating the pathways that disrupt NVU homeostasis, especially those compounded by comorbidities, and how oxidative stress and mitochondrial dysfunction contribute to this disruption. Identifying early biomarkers of vascular dysregulation and the factors priming the vasculature for stroke is of great interest, alongside mechanistic insights into modifiable risks (e.g., hypertension, diabetes) and predictive models for personalized interventions. Particular attention will be given to investigations addressing the production of reactive oxygen species (ROS), the resulting oxidative damage during cerebral ischemia–reperfusion, and neuroprotective interventions (such as antioxidants) that preserve mitochondrial integrity and NVU health.

o Blood–Brain Barrier Disruption: Defining ischemia-induced oxidative and enzymatic cascades leading to BBB breakdown and microvascular injury. Mechanistic studies investigating processes such as matrix metalloproteinase release by microglia, and approaches to protect or repair the BBB, are highly relevant.

We emphasize studies with clear translational impact, including consideration of ethical issues and equitable access to novel interventions. Mechanistic discoveries should be implementable in clinical practice, and discussions of strategies to reduce health disparities are encouraged. Our aim is to foster a paradigm shift in stroke research and care, grounded in mechanistic understanding, interdisciplinary collaboration, and patient-centered innovation.

Impact

Frontiers in Stroke

Mechanisms, Models, and Biomarkers of Stroke