Investigation of Potential Therapeutic Application of Thioredoxin Therapy for Enhancement of NPCs Proliferation After Stroke

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Alysa, Almojuela
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Stroke is a leading cause of death and disability in Canada. The acute management of stroke involves the use of thrombolytics and/or mechanical recanalization. Despite successful implementation of these techniques, limited therapeutic benefits emphasize a current need for novel treatments. The presence of endogenous neural precursor cells (NPCs) in the subventricular zone of the adult human central nervous system represents a potential therapeutic cell source in the setting of stroke. These NPCs have a limited capacity to replace neurons, astrocytes and oligodendrocytes in response to stroke, but tissue demand ultimately exceeds this proliferative capacity. In this project, we show that thioredoxin (Trx) treatment enhances NPC proliferation and modifies their differentiation. Application of Trx in an in-vitro model of NPC culture induced cell proliferation. The effect of Trx on NPC differentiation was investigated using cell specific immunocytochemistry, which displayed significantly higher numbers of oligodendrocyte (Oiig2+ cells) and lower numbers of GFAP+ cells in Trx pre-treated cultures. To investigate the effects of Trx in-vivo, a focal permanent devascularisation lesion (stroke) was implemented in experimental rat models, and Trx was delivered after intraventricular infusion. Immunohistochemistry revealed enhanced NPC proliferation in animals that received Trx treatment versus animals that received the vehicle, as indicated by the presence of significantly higher levels of proliferation marker (BrdU) and stem cells (Sox2) expressing cells in both the subventricular zone and cortex. Ultimately, these results highlight Trx as a potential neuroprotective therapy in the setting of stroke that can enhance the endogenous NPC proliferation.
stroke, thopredoxin (Trx)