Lentivirus-mediated microRNA-26a-modified neural stem cells improve brain injury in rats with cerebral palsy

J Cell Physiol. 2020 Feb;235(2):1274-1286. doi: 10.1002/jcp.29043. Epub 2019 Jul 2.

Abstract

This study is launched to investigate the effect of lentivirus-mediated microRNA-26a (miR-26a)-modified neural stem cells (NSCs) in brain injury in rats with cerebral palsy (CP). The successfully constructed miR-26a lentivirus expression vector and empty vector virus were used to modify NSCs. The model of CP with ischemia and anoxia was established in rats. NSCs and miR-26a-NSCs were stereoscopically injected into the cerebral cortex of the modeled rats, respectively. The survival and migration of NSCs infected with recombinant lentivirus expressing green fluorescence in vivo was observed under a light microscope. The neurobehavioral functions, morphology, and ultrastructure of cerebral cortex and hippocampus, apoptosis of brain cells, expression of apoptosis-related protein caspase-3 and Bax, together with the expression of the glial fibrillary acidic protein (GFAP) in cerebral cortex and hippocampus were determined. Expression of miR-26a in NSCs infected with plVTHM-miR-26a increased significantly. After NSCs transplantation, the neurobehavioral status of CP rats was improved, the degree of brain pathological injury was alleviated, the apoptotic index of cells in cerebral cortex and hippocampus and the expression of the apoptotic protein (caspase-3 and Bax) were decreased, the expression of GFAP were significantly decreased. After miR-26a-NSCs transplantation, these aforementioned results further improved or decreased. Our study suggests that miR-26a-modified NSCs mediated by lentivirus can improve brain injury, inhibit apoptosis of brain cells and activation of astrocytes in CP rats.

Keywords: apoptosis; astrocyte; cerebral palsy; gene modification; glial fibrillary acidic protein; microRNA-26a; neural stem cells; neurobehavioral function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Cerebral Palsy / metabolism
  • Cerebral Palsy / pathology*
  • Genetic Vectors
  • Lentivirus
  • MicroRNAs / genetics*
  • Neural Stem Cells / transplantation*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation / methods*

Substances

  • MIRN26 microRNA, rat
  • MicroRNAs