Extracellular Vesicles and Ischemic Brain Injury

Extracellular vesicles including microvesicles and exosomes are nanometer-sized vesicles released from cells into the blood, where they can transmit signals throughout the body. These vesicles contain materials that can reflect the genetic and proteomic information of the secreting cell. Additionally, in recent years it was noted that exosomes from stem cells delivered via peripheral blood might benefit neurological disorders. We hypothesize that exosomes from neuronal cells convey valuable genetic and proteomic information which reflects the cellular and molecular alteration under hypoxia/ischemia and may be used for biomarker development to predict the prognosis and may hold the therapeutic potential to change cells fate. We also hypothesize that medications with neuroprotective characters may affect exosomes secretion, regulate the content of exosomes and lessen ROS or inflammation status under ischemia-induced neuronal injury. The objectives of this proposal are 1) to define the potential roles of exosomes as biomarkers development and 2) to explore the potential therapeutic advancement of exosomes in cerebral ischemia. These will be accomplished by using both in vitro and in vitro ischemic models including oxygen-glucose deprivation (OGD) and transient focal cerebral ischemia models. Exosomes collected from cultures medium and peripheral blood will be verified for particle size by electron microscopy (EM) and Nanoparticle Tracking Analysis as well as the exosomes marker such as tetraspanins, TSG101, and Alix by Western blotting. For extraction of the neural-derived exosome, each exosomes suspension will be incubated with anti-neural cell adhesion molecule-1 (NCAM-1) or anti-neural cell adhesion molecule L1 (L1CAM) antibodies. Exosomes and neural-derived exosomes will be analyzed for miRNA or proteomic studies. Information from these exosomes will offer more insight about molecules to exert protective effects during ischemic condition. We will also test the potential of exosomes transfer which will be collected from culture medium after certain medications or neurotrophic factors treatment and used both in vitro and in vivo ischemic models. Overall, a potential biomarker involving either detrimental or protective mechanism under cerebral ischemia may be obtained, and exosomes transfer as a therapeutic potential may emerge and endow a rationale to develop new therapeutic regimens for cerebral ischemia.

Project ID:PC10608-1471
External Project ID:MOST106-2314-B182-031