Differential Effects of Young and Old Serum Exosomes on Ischemic Stroke Outcomes in Aged Rats
Background: Aging is associated with striking increases in the incidences of stroke and neurodegenerative diseases, both of which are major causes of disability among those age 70 years and older in the United States. Despite progress in understanding molecular mechanisms of neuronal cell death after stroke, effective treatment remains elusive. Recent studies showed that systemic factors in the blood can profoundly reverse aging-related impairments, and our study show that aging systemic milieu could worse outcome after ischemic stroke in rats. However, the underlying mechanism remain unclear. Exosomes are extra-cellular microvesicles that play important roles in intercellular signaling and in regulating various physiological and pathological conditions. Here, we explore the role of young and old serum-derived exosomes on ischemic outcome in aged rats. Method: The exosomes were isolated from serum of young or old rats, and then were intravenously injected into aged ischemic rats via tail for 3 days, respectively. Infarct volume was determined with triphenyltetrazolium chloride (TTC) staining and motor function was assessed with neurobehavioral tests including running ladder and cylinder tests. To elucidate the potential mechanism underlying the functional improvement or deterioration, neuroplasticity was examined after treatment of young and old serum exosomes using Golgi-Cox staining and data were analyzed using Imaris software. Results: We found that injection of young serum exosomes into aged ischemic rats reduced infarct volume and improved motor functional deficits. On the contrary, injection of old serum exosomes increased infarct volume and worsened motor function. We also found that the dendritic length and spine numbers were significantly increased after injection of young exosomes, while decreased after injection of old exosomes. Conclusion: Our data suggest that young and old serum exosomes differentially affect functional outcome in aged rats after ischemic stroke, which potentially be translated into novel therapeutic intervention by minimizing the destructive potential of detrimental molecules and enhancing the beneficial contributions to repair the damaged brain.