Plasma Levels of Neuron/Glia-Derived Apoptotic Bodies, an In Vivo Biomarker of Apoptosis, Predicts Infarct Growth and Functional Outcome in Patients with Ischemic Stroke.

Abstract

Evidence demonstrating the involvement of apoptosis in the death of the potentially salvageable area (penumbra zone) in patients during stroke remains limited. Our aim was to investigate whether apoptotic processes occur in penumbral brain tissue by analyzing circulating neuron- and glia-derived apoptotic bodies (CNS-ApBs), which are vesicles released into the bloodstream during the late stage of apoptosis. We have also assessed the clinical utility of plasma neuronal and glial apoptotic bodies in predicting early neurological evolution and functional outcome. The study included a total of 71 patients with acute hemispheric ischemic stroke (73 ± 10years; 30 women). Blood samples were collected from these patients immediately upon arrival at the hospital (within 9h) and at 24 and 72h after symptom onset. Subsequently, isolation, quantification, and phenotypic characterization of CNS-ApBs during the first 72h post-stroke were performed using centrifugation and flow cytometry techniques. We found a correlation between infarct growth and final infarct size with the amount of plasma CNS-ApBs detected in the first 72h after stroke. In addition, patients with neurological worsening (progressive ischemic stroke) had higher plasma levels of CNS-ApBs at 24h after symptom onset than those with a stable or improving course. Circulating CNS-ApB concentration was further associated with patients' functional prognosis. In conclusion, apoptosis may play an important role in the growth of the cerebral infarct area and plasma CNS-ApB quantification could be used as a predictive marker of penumbra death, neurological deterioration, and functional outcome in patients with ischemic stroke.