Abstract

Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI). Recently, stem cell therapy has emerged as a new avenue to address neuronal regeneration after TBI. However, the environment of TBI lesions exerts negative effects on the stem cells efficacy. Therefore, to maximize the beneficial effects of stem cells in the course of TBI, we evaluated the effect of human neural stem/progenitor cells (hNS/PCs) and curcumin-loaded niosome nanoparticles (CM-NPs) on behavioral changes, brain edema, gliosis, and inflammatory responses in a rat model of TBI. After TBI, hNS/PCs were transplanted within the injury site and CM-NPs were orally administered for 10 days. Finally, the effect of combination therapy was compared to several control groups. Our results indicated a significant improvement of general locomotor activity in the hNS/PCs + CM-NPs treatment group compared to the control groups. We also observed a significant improvement in brain edema in the hNS/PCs + CM-NPs treatment group compared to the other groups. Furthermore, a significant decrease in astrogliosis was seen in the combined treatment group. Moreover, TLR4-, NF-κB-, and TNF-α- positive cells were significantly decreased in hNS/PCs + CM-NPs group compared to the control groups. Taken together, this study indicated that combination therapy of stem cells with CM-NPs can be an effective therapy for TBI.

Highlights

  • Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI)

  • Our findings showed that significant neuroprotective effects were seen in the human neural stem/progenitor cells (hNS/PCs) + curcumin-loaded niosome nanoparticles (CM-NPs) treatment group compared to the control groups in terms of “general locomotor activity” after brain injury

  • Brain edema showed significant improvement in the hNS/PCs + CM-NPs treatment group compared to all other groups

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Summary

Introduction

Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI). Among different types of stem cells, numerous studies have demonstrated that neural stem cells (NSCs) transplantation has great neuroprotective properties that support functional recovery after acute TBI by mitigation of neuroinflammation and by the promotion of regenerative processes (i.e., increase neurogenesis, angiogenesis, and plasticity)[17–19]. Encapsulation of therapeutics within nanoparticles (NPs) is one of the approaches that can improve site-specific delivery and b­ ioavailability[26] In this regard, the aim of this study was to investigate human NSCs transplant in a TBI model with nanoparticles containing anti-inflammatory agents. We show for the first time that combining NSCs derived from the human fetal brain with CM-NPs has the potential to improve functional recovery and reduce neuroinflammation in a TBI model by mitigating TLR4/NF-κB pathway

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