BMSCs attenuate radiation-induced brain injury induced hippocampal neuronal apoptosis through a PI3K/Akt/Bax/Bcl-2 signaling pathway

Kaina Xu; Zhanhong Liu; Shichao Pan; Na Zhang; Shuang Wu; Guangrun Yang; Xue Song; Ye Teng; Xu Tong

doi:10.1016/j.brainres.2024.148795

BMSCs attenuate radiation-induced brain injury induced hippocampal neuronal apoptosis through a PI3K/Akt/Bax/Bcl-2 signaling pathway

Brain Res. 2024 Apr 15:1829:148795. doi: 10.1016/j.brainres.2024.148795. Epub 2024 Feb 7.

Authors

Kaina Xu¹, Zhanhong Liu¹, Shichao Pan¹, Na Zhang¹, Shuang Wu², Guangrun Yang², Xue Song², Ye Teng², Xu Tong³

Affiliations

¹ College of Medical Technology, Qiqihar Medical University, No.333 Bukui Street, Jianhua District, Qiqihar, Heilongjiang 161006, China.
² Department of Radiotherapy, The Third Affiliated Hospital of Qiqihar Medical University, No.27, Taishun Street, Tiefeng District, Qiqihar, Heilongjiang 161006, China.
³ Department of Radiotherapy, The Third Affiliated Hospital of Qiqihar Medical University, No.27, Taishun Street, Tiefeng District, Qiqihar, Heilongjiang 161006, China. Electronic address: cn_tongxu@163.com.

PMID: 38331376
DOI: 10.1016/j.brainres.2024.148795

Abstract

Background: Bone marrow mesenchymal stem cell (BMSCs) -based therapies represent a promising treatment for neurological disorders. However, therapeutic effects and mechanisms of BMSCs transplantation for radiation-induced brain injury (RIBI) have not been fully disclosed. In this article, we explored the functions of BMSCs transplantation on RIBI and investigated the protective effects of BMSCS on hippocampal neurons in RIBI as well as the related molecular mechanisms.

Materials and methods: 6-8 weeks-old rats were used to build a RIBI model. Rats in BMSC group were treated with a 3 × 10⁶ BMSCs injection through the tail vein on the 1st day and 8th day after irradiation; rats in both control and RIBI groups were injected with an equivalent volume of physiological saline for comparisons. The Morris water maze was applied to detect the variations in cognitive function after RIBI. MRS was performed to test changes in NAA/Cr, indicating neuronal apoptosis after RIBI. TUNEL was conducted to detect apoptosis of rat hippocampal neurons, and HE staining was carried out to show pathological variations in the hippocampal region of rats. Protein levels of PI3K, P-PI3K, AKT, P-AKT, Bcl-2, and Bax proteins of rats in the hippocampal area were all determined by Western blot.

Results: Cognitive function was reduced and hippocampal neurons underwent apoptosis in the rats of the RIBI group, and cognitive abilities, histopathological alterations, and apoptosis of hippocampal neurons were significantly improved after BMSCs treatment; the expression of PI3K, P-PI3K, AKT, P-AKT, and Bcl-2 proteins, in the hippocampal region of the rat, was up-regulated, and Bax proteins were down-regulated.

Conclusions: BMCSs can inhibit hippocampal neuronal apoptosis in RIBI, and the mechanism may be associated with the up-regulation of Bcl-2 and down-regulation of Bax by the PI3K/AKT signaling pathway.

Keywords: Apoptosis; Bone marrow mesenchymal stem cells; Hippocampal neurons; PI3K/AKT/Bax/Bcl-2 signaling pathway; Radiation-induced brain injury.

MeSH terms

Animals
Apoptosis
Brain Injuries* / metabolism
Hippocampus / metabolism
Mesenchymal Stem Cells* / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction
bcl-2-Associated X Protein / metabolism

Substances

Proto-Oncogene Proteins c-akt
bcl-2-Associated X Protein
Phosphatidylinositol 3-Kinases