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

Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE

Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-

Astrocytes/*cytology ; Brain Infarction/*physiopathology ; Mesenchymal Stem Cell Transplantation/*methods ; Tumor Necrosis Factor-alpha/*metabolism; Animals ; Brain Infarction/therapy ; Brain Ischemia/physiopathology ; Brain Ischemia/therapy ; Disease Models, Animal ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Male ; Microglia/cytology ; Rats ; Rats, Sprague-Dawley

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.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Keywords: Astrocyte; Cerebral Ischemia; Mesenchymal Stem Cell transplantation; Microglia; Tumor Necrosis Factor-α

0 (Tumor Necrosis Factor-alpha)

Date Created: 20210803 Date Completed: 20220106 Latest Revision: 20220106

20240829

10.1016/j.biopha.2021.111971

34343893