Myeloid—Vascular Crosstalk as a Regulator of Secondary Brain Injury After Stroke 2310349

Abstract

Abstract Introduction Secondary brain injury after stroke is a major factor in neurological outcomes, yet the mechanisms behind it remain poorly understood. Evidence suggests interactions between myeloid cells (both circulating and resident) and the blood—brain barrier (BBB) may explain inflammatory patterns and region-specific vulnerability. We explored this “myeloid-vascular crosstalk” as a framework to understand secondary injury. Understanding these interactions could help identify high-risk patients and guide early treatment. Methods We conducted a systematic review and meta-analysis (PRISMA) of studies from 1990—2025 examining inflammatory biomarkers in ischemic or hemorrhagic stroke. Biomarkers included serum, CSF, and tissue-level measures reflecting myeloid activation, endothelial signaling, or immune trafficking. Using a Bayesian hierarchical model, we assessed links between biomarker trajectories and secondary injury outcomes such as edema, hemorrhagic transformation, and neurological decline. Results Across heterogeneous stroke cohorts, indicators of myeloid activation (specifically circulating monocytes, IL-1β, TNF-α) demonstrated stronger and consistent associations with secondary brain injury than endothelial markers alone. Experimental data suggests post-stroke endothelial activation triggers myeloid recruitment, thereby amplifying vascular permeability. Despite differences in biomarker timing, cumulative evidence establishes immune activation as a key mediator of secondary injury progression. Conclusion Our findings support that myeloid—vascular crosstalk plays a role in secondary brain injury after stroke. Posterior circulation and deep subcortical regions appear especially vulnerable, suggesting that early modulation of immune—vascular interactions could reduce severe complications. This study supports a coordinated myeloid-vascular framework, rather than single biomarkers, to help improve risk stratification and guide future targeted immunomodulatory therapies. Funding Source n/a Topic Categories Neuroimmunology (NEUR)