Transplantation of bone mesenchymal stem cells promotes angiogenesis and improves neurological function after traumatic brain injury in mouse

Shewei Guo,* Yingwei Zhen,* Anran Wang Department of Neurosurgery, The First Affiliated Hospital, Zhengzhou University, Henan, China *These authors contributed equally to this work Abstract: Traumatic brain injury (TBI) has emerged as a leading cause of mortality and morbidity worldwide. Transplantation of bone mesenchymal stem cells (BMSCs) has emerged as a promising treatment for various central nervous system diseases. This study aims to evaluate the effect of BMSCs transplantation by intravenous injection on neurological function and angiogenesis of the TBI mice. C57BL/6 male mice were randomly divided into four groups: control, sham, TBI, and BMSC. Functional neurological evaluation was performed 1, 4, 7, 14, and 21 days after TBI using neurological severity scores. The impairment of learning and memory in mice was evaluated 14 days after TBI by Morris water maze experiment. Mice were sacrificed 14 days after TBI, and then brain sections were stained by terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling staining to assess brain neuronal apoptosis. Immunohistochemistry was conducted to evaluate caspase-3 activity and identify vascular distribution and microvessel density. Protein and mRNA levels of vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) in brain tissues were analyzed by Western blot and quantitative real-time polymerase chain reaction, respectively. BMSCs transplantation promoted recovery of neurological function, ameliorated impairment of learning and memory, attenuated neuronal apoptosis, and diminished caspase-3 activation in mice after TBI. Also, BMSCs transplantation upregulated expressions of VEGF and Ang-1 and promoted the formation of microvessels in brain tissues after TBI. Our study demonstrated the important role of BMSCs transplantation in TBI mouse and indicated that the underlying mechanism was through promoting angiogenesis and improving neurological function. This provides a novel and effective strategy for cell-based therapy in the treatment of TBI. Keywords: TBI, BMSCs, angiogenesis, neurological function&nbsp