Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

Background: As a form of biological therapy, placenta-derived mesenchymal stem cells (PDMSCs) exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury (TBI) due to their multi-target and multi-pathway mode of action. Material & Methods: This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact (CCI) in rats and glutamate-induced oxidative stress injury in HT22 cells in vitro. Our primary objective is to provide evidence supporting the clinical application of PDMSCs. Results: In the in vivo arm of our investigation, we observed a swift elevation of matrix metalloproteinase-9 (MMP-9) in the proximal cortex of injured brain tissues after CCI. PDMSCs, distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and -2 (TIMP-1 and TIMP-2): were intravenously administered via the caudal vein. This intervention yielded significant reductions in the permeability of the blood-brain barrier (BBB): the extent of brain edema, the levels of inflammatory cytokines IL-1 beta and TNF-alpha in damaged brain tissue, and the activation status of microglia in CCI-afflicted rats. In the realm of in vitro experiments, PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional media. Notably, this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and TIMP-2. Conclusion: Collectively, our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.