Abstract
BackgroundLittle is known about the effects of induced pluripotent stem cell (iPSC) treatment on acute cerebral inflammation and injuries after intracerebral hemorrhage (ICH), though they have shown promising therapeutic potentials in ischemic stoke.MethodsAn ICH model was established by stereotactic injection of collagenase VII into the left striatum of male Sprague-Dawley (SD) rats. Six hours later, ICH rats were randomly divided into two groups and received intracerebrally 10 μl of PBS with or without 1×106 of iPSCs. Subsequently, neural function of all ICH rats was assessed at days 1, 3, 7, 14, 28 and 42 after ICH. Inflammatory cells, cytokines and neural apoptosis in the rats’ perihematomal regions, and brain water content were determined on day 2 or 3 post ICH. iPSC differentiation was determined on day 28 post ICH. Nissl+ cells and glial fibrillary acidic protein (GFAP)+ cells in the perihematoma and the survival rates of rats in two groups were determined on post-ICH day 42.ResultsCompared with control animals, iPSCs treatment not only improved neurological function and survival rate, but also resulted in fewer intracephalic infiltrations of neutrophils and microglia, along with decreased interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α), and increased IL-10 in the perihematomal tissues of ICH rats. Furthermore, brain oedema formation, apoptosis, injured neurons and glial scar formation were decreased in iPSCs-transplanted rats.ConclusionsOur findings indicate that iPSCs transplantation attenuate cerebral inflammatory reactions and neural injuries after ICH, and suggests that multiple mechanisms including inflammation modulation, neuroprotection and functional recovery might be involved simultaneously in the therapeutic benefit of iPSC treatment against hemorrhagic stroke.
Highlights
Intracerebral haemorrhage (ICH) is a serious stroke subtype associated with high morbidity, mortality, disability and recurrence rate [1,2,3]
Our findings indicate that induced pluripotent stem cell (iPSC) transplantation attenuate cerebral inflammatory reactions and neural injuries after intracerebral hemorrhage (ICH), and suggests that multiple mechanisms including inflammation modulation, neuroprotection and functional recovery might be involved simultaneously in the therapeutic benefit of iPSC treatment against hemorrhagic stroke
We previously reported that the transplantation of human iPSCs at 24 hours. after ICH can give rise to better functional recovery in rats with experimental ICH, and suggested that cell replacement and/or neurotrophic action may be involved in the therapeutic effects of iPSCs treatment for ICH[24]
Summary
Intracerebral haemorrhage (ICH) is a serious stroke subtype associated with high morbidity, mortality, disability and recurrence rate [1,2,3]. Accumulating evidence has shown that cerebral inflammatory responses, including the infiltration of inflammatory cells such as neutrophils and mononuclear-macrophages, microglial activation and the secretion of inflammatory-related cytokines, play a crucial role in all phases of the ICH-induced secondary brain damages. This data suggests that various inflammatory pathways involving specific mediators and inflammatory cells may be as promising therapeutic targets for treating ICH [1, 3,4,5,6,7,8]. Little is known about the effects of induced pluripotent stem cell (iPSC) treatment on acute cerebral inflammation and injuries after intracerebral hemorrhage (ICH), though they have shown promising therapeutic potentials in ischemic stoke.
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