Astrocytes constitute the major TNF-α-producing cell population in the infarct cortex in dMCAO rats receiving intravenous MSC infusion

Yunqian Guan, Ren Wang, Xiaobo Li, Haiqiang Zou, Wenxiu Yu, Zhaohui Liang, Lei Li, Ling Chen, Liping Zhou, Zhiguo Chen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

4 Citations (Scopus)

Abstract

Recent studies report that inhibiting TNF-α might be a novel therapeutic strategy for managing brain ischemia. Our previous study reported that mesenchymal stem cell (MSC) transplantation could suppress TNF-α level in both serum and brain. However, the cell type(s) that contribute to the production of TNF-α during ischemia following MSC transplantation has not been well studied. In the present study, we found by fluorescent immunohistochemistry, that 7.95 ± 6.17% of TNF-α+ cells co-expressed Iba-1 in the infarct area of dMCAO rats, a majority of which were found to be CD68+ (activated microglia), suggesting that resident microglial population were not the major source of TNF-α expression. 68.49 ± 5.12% of the TNF-α+ cells in the infarct area could be labeled by GFAP, a specific marker for astrocytes, indicating that resident GFAP+ astrocytes might be the major source of TNF-α expression in the infarct area. In addition to the infarct area, the GFAP+/TNF-α+ double-positive astrocytes accounted for 73.68 ± 7.48% of the TNF-α+ cells in striatum and corpus callosum. The infiltrating cells, including monocytes and lymphocytes, were not the main source of TNF-α either. In response to MSC transplantation, the total TNF-α+ cells as well as the percentage of TNF-α-expressing astrocytes were significantly reduced in the infarct area, suggesting that MSC transplantation could suppress the expression of TNF-α by astrocytes. Taken together, the results demonstrated that resident astrocytes, but not microglia, were the major source of TNF-α expression and could be suppressed by MSC infusion.

Original languageEnglish
Article number111971
JournalBiomedicine and Pharmacotherapy
Volume142
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Astrocyte
  • Cerebral Ischemia
  • Mesenchymal Stem Cell transplantation
  • Microglia
  • Tumor Necrosis Factor-α

ASJC Scopus subject areas

  • Pharmacology

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