Investigation of Potential Therapeutic Application of Thioredoxin Therapy for Enhancement of NPCs Proliferation After Stroke
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Date
2014-08-08
Authors
Alysa, Almojuela
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Abstract
Description
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.
Keywords
stroke, thopredoxin (Trx)