Blood vessel wall biomarkers and functional recovery in stroke and anxiety disorders

Abstract

Background and aims: Stroke afflicts about 25000 individuals annually in Sweden, many becoming functionally dependent and roughly one third suffering from post-stroke depression or anxiety. Meanwhile, mental health continues to deteriorate with a point prevalence of nearly 15% in Sweden for clinically significant anxiety, which is also a risk for stroke. Experimental studies on ischemic stroke and anxiety/depression have shown promise for granulocyte-colony stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF). Both factors are neuroprotective agents and may be mediators of local neurogenesis and angiogenesis. Exploring these may present better rationale for lifestyle and pharmacological interventions. The aim was therefore to investigate the relevance of serum G-CSF and VEGF in human stroke and anxiety cohorts. Methods: Studies I and II assessed post-stroke functional outcome in an observational study on ischemic stroke. Studies III and IV evaluated functional recovery in patients with anxiety disorders after an exercise intervention. Results: Higher endogenous serum VEGF (Study I) and G-CSF (Study II) were independently associated with poor functional outcome after ischemic stroke. In addition, although functional recovery in health-related quality of life was observed after 12 weeks of exercise in patients with anxiety (Study III), neither serum G-CSF nor VEGF was elevated, nor did they mediate functional recovery (Study IV). However, there were numerous small-to-moderate correlations between serum G-CSF/VEGF and inflammation parameters in both cohorts (Studies I, II, and IV). Conclusions: In Studies I and II, G-CSF and VEGF were associated with poor post-stroke functional outcome, which may be explained by the associations between inflammation and increased stroke severity. Also, although exercise led to long-term functional recovery in Studies III and IV, the absence of mediation by G-CSF and VEGF may reflect different actions in serum compared with those previously observed in experimental studies.