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Background: Extensive loss of donor neural stem cell (NSCs) due to ischemic stress and low rate of differentiation at
the site of cell graft are two of the major issues that hamper optimal outcome in NSCs transplantation studies. Given
that histone deacetylases (HDACs) modulate various cellular processes by deacetylating histones and non-histone
proteins, we hypothesized that combined treatment with small molecules, sodium butyrate (NaB; a known HDAC
inhibitor) and nicorandil, will enhance the rate neuronal differentiation of NSCs besides their preconditioning to resist
oxidative stress.
Methods: NSCs derived from 14-day old Sprague Dawley rat ganglion eminence were characterized for tri-lineage
differentiation. Treatment with 1 mM NaB significantly changed their culture characteristics while continuous treatment
for 10 days enhanced their neural differentiation. NaB treatment also preconditioned the cells for their resistance to
oxidative stress.
Results: The highest rate of neural differentiation and preconditioning effect was achieved when the NSCs were
treated concomitantly with NaB and nicorandil. Cell proliferation assay showed that concomitant treatment with NaB
and nicorandil retarded their rate of proliferation.
Conclusion: These data conclude that preconditioning of NSCs with NaB and nicorandil effectively enhances their
differentiation capacity besides preconditioning the cells to support their survival under ischemic conditions