mNSCs overexpressing Rimkla transplantation facilitates cognitive recovery in a mouse model of traumatic brain injury

Published: 25 August 2023| Version 1 | DOI: 10.17632/5pd72p7n4m.1
Chunlong Zhong


N-acetyl aspartyl-glutamate (NAAG) is easily inactivated by the hydrolysis of NAAG peptidase (GCPII) on the surface of glial cells, thereby losing the endogenous neuroprotection after traumatic brain injury. In recent years, the transplantation of genetically modified neural stem cells (NSCs) has made encouraging progress in reducing brain damage and promoting the recovery of brain function after traumatic brain injury (TBI). In this study, mouse embryonic neural stem cells (mNSCs) were used to over-express/knock out NAAG synthase (Rimkla) in vitro using lentiviral vectors and transplanted into the hippocampus of mice with controlled cortical impact (CCI). In vivo experiments showed that transplantation of mNSCs overexpressing Rimkla improved glutamine-glutamate cycling between astrocytes and neurons in the subacute phase of CCI, thereby enhancing neuronal metabolic support and promoting neuronal synaptic repair in the hippocampal CA3 region, and finally promoting the recovery of learning and memory in mice. Taken together, these findings confirm that overexpression of NAAG synthetases in neural stem cells can effectively maintain NAAG concentrations in local brain regions, which opens up new ideas for the maintenance of NAAG neuroprotective effects after TBI and provides a new strategy for the treatment of traumatic brain injury with neural stem cell transplantation. RNA sequencing data were divided into mNSCs-Vector and mNSCs-Rimkla-OE groups. The hippocampal tissues of the injection side were taken for sequencing on the 7th day after injection of neural stem cells into the traumatic brain injury model mice. There were three samples in each group.



Tongji University School of Medicine


Neurosurgery, Traumatic Injury, Neural Stem Cell