Abstract TP13: Beneficial Effects Of Exercise On Functional Outcome After Ischemic Stroke: A New Insight On Astrocytes Activation And Cellular Crosstalk

Abstract

Introduction: It has been recognized that astrocytes potentially affect the recruitment and function of neurons, and the interactions among astrocytes, microglia and neurons modulate neuroplasticity and neural circuit function. The present study attempted to explore whether astrocytes activation and cellular crosstalk were involved in neuroplasticity and neurorehabilitation. Methods: Sprague-Dawley adult rats were subjected to 2 h middle cerebral artery occlusion followed by reperfusion. Treadmill exercise (15m/min) was initiated 24 h after reperfusion for up to 21 days. Rats were assigned to groups entailing post-stroke rest or exercise for 30 min. Motor and cognitive functions were tracked. Western blotting was used to assess the proteins expression for neuroplasticity, including GAP-43, PSD-95 and BDNF. Immunofluorescence was used to assess astrocyte proliferation. Primary cells co-cultivation were used to determine the interaction of astrocyte and microglia by IL-33/ST2 interplays, and interaction of microglia and neuron by BDNF/TrkB interplays. The interactions affected by exercise were detected by Co-IP in ischemic rats. Besides, D-serine release by ELISA and NMDAR receptor expression were used to assess astrocyte-neuron direct communication. Results: Physical exercise significantly induce neuroplasticity and functional outcomes in ischemic rats, in association with astrocyte proliferation. Exercise induced IL-33/ST2 and BDNF/TrkB interplays in rats, suggesting the increasing astrocyte-microglia and microglia-neuron crosstalk. Exercise significantly increase astrocyte D-serine release and neural NMDAR expression, indicating the direct crosstalk in astrocyte and neuron. Primary cells co-cultivation further demonstrated the IL-33/ST2 interplays showing astrocyte-microglia crosstalk and BDNF/TrkB interplays showing microglia-neuron communication. Conclusion: These findings indicated beneficial effects of long-term treadmill exercise on neuroplasticity and functional outcome. Importantly, the results showed astrocyte activation and interaction with microglia and neuron in the biochemical processes underlying the exercise-induced post-stroke neuroplasticity and neurorehabilitation.