New Perspectives on Stroke: The Immune-inflammatory-mitochondrial Axis

To delineate the distinct immunoregulatory and mitochondrial characteristics in patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH).

We conducted a cross-sectional study (34 AIS, 27 ICH, 30 controls) and a dynamic tracking study (1 AIS, 1 ICH). T-cell subpopulations, mitochondrial mass (MM), low mitochondrial membrane potential (MMPlow, %), and cytokine profiles were analyzed. Limitations include the small dynamic cohort and potential treatment-related confounding.

The percentages of T regulatory lymphocytes (Treg%) and effector T regulatory lymphocytes (eTreg%) were significantly higher in AIS patients than in ICH patients (p = 0.029, p = 0.017) and correlated with disease severity in AIS patients (p = 0.024, p = 0.014). The IL-10/IL-6 ratio was significantly higher in AIS than in ICH patients (p = 0.004). AIS patients exhibited predominant changes in CD4+ (T4) lymphocyte subsets, whereas ICH patients showed more pronounced alterations in CD8+ (T8) subsets, with corresponding mitochondrial damage observed in T-cells in both groups.

Despite limitations from the small dynamic cohort and inherent clinical confounders, this study demonstrates that AIS and ICH are characterized by distinct and evolving immune- inflammatory-mitochondrial axes. These preliminary findings highlight the role of Treg cells in AIS and suggest divergent T-cell subset involvement, providing a rationale for developing subtype-specific therapeutic strategies targeting the immune-mitochondrial axis.

Our study delineates a distinct immune-inflammatory-mitochondrial axis in stroke, characterized by predominant CD4+ involvement in AIS versus CD8+ T-cell alterations in ICH. These findings underscore the potential for immunomodulatory and mitochondrial-protective strategies tailored to specific stroke subtypes.