Therapeutic effect and mechanism of bone marrow mesenchymal stem cell-derived exosomes on traumatic brain injury through the ERK signaling pathway

Introduction
The aim of this study was to investigate the effect and possible mechanism of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) on traumatic brain injury (TBI) in order to provide new strategies for clinical treatment of TBI.

Material and methods
Thirty-two healthy male rats were randomly divided into the control group, model group, model control group, and mesenchymal stem cell (MSC) exosome group, with 8 rats in each group. TBI model rats were established using Feeney’s free-falling method. Bone marrow mesenchymal stem cells were isolated and cultured, their exosomes were extracted, and MSC exosomes were injected into the bilateral medial hippocampus of rats in the model control group and MSC exosome group. A Morris water maze was used to detect behavioral indicators in each group; hematoxylin-eosin (HE) staining was used to observe the morphological changes of rat hippocampal neurons; an immunohistochemical method was used to detect the expression of the protein Erk/P-Erk in the Erk signaling pathway of rat hippocampal cells; RT-PCR and Western blot were used to detect the mRNA and protein expression levels of b-catenin and cyclin D1.

Results
Compared with the model control group, the MSC exosome group showed a reduced escape latency, as well as an increased number of platform crossings and longer time spent in the platform quadrant. Compared with the model group and the model control group, the lateral compartments of brain tissue in rats in the MSC exosome group did not widen significantly. The arrangement gradually became orderly and compact, with some local areas of looseness remaining, but overall structural improvement was observed. The Erk/P-Erk, and b-catenin levels in the MSC exosome group increased, and the cyclin D1 level decreased.

Conclusions
BMSC-Exo have a significant therapeutic effect on TBI by upregulating the expression of proteins related to the ERK signaling pathway and regulating neuron-related proteins and cell proliferation, which provides a potential new strategy for the treatment of TBI.