Neural Stem Cell Transplantation Promotes Functional Recovery From Traumatic Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity

Mol Neurobiol. 2018 Mar;55(3):2696-2711. doi: 10.1007/s12035-017-0551-1. Epub 2017 Apr 18.

Abstract

Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 105/μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-β were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats.

Keywords: Brain-derived neurotrophic factor; Neural stem cell transplantation; RNA knockdown; Synaptophysin; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / therapy*
  • Brain-Derived Neurotrophic Factor / deficiency
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cells, Cultured
  • Female
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / transplantation*
  • Neuronal Plasticity / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / physiology
  • Stem Cell Transplantation / methods*

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor