ABSTRACT
Objective·To investigate the effect of mesenchymal stem cells (MSCs) on autophagy in hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods·Western blotting was used to detect the expression levels of autophagy associated proteins Beclin1, LC3 Ⅱ , and p62 in the hippocampus of HIBD rats following MSCs transplantation and oxygen glucose deprivation (OGD)-injured primary neurons following MSCs seperated coculture. The learning-memory function in the HIBD rats after MSCs transplantation was tested by Morris water maze test. Transmission electron microscopy was also used to observe the number of autophagic neurons in OGD damaged neurons after coculture with MSCs. Results·The levels of Beclin1 and LC3 Ⅱ protein expressions were significantly increased at 12-24 h in the rat hippocampus following HIBD injury. MSCs transplantation statistically downregulated the autophagy level in the hippocampus, and obviously improved the learning-memory function of HIBD rats. Meanwhile, the levels of Beclin1 and LC3 Ⅱ protein expressions in the primary neurons in vitro were also induced by OGD for 12 h. MSCs seperated coculture significantly downregulated the autophagy level of hippocampal neurons by OGD injury, decreased the number of autophagosome in the OGD-injured neurons. Conclusion·MSCs may inhibit the autophagy of hippocampal neurons by partly regulating the damaged microenvironment to improve the learning and memory function of HIBD rats.