Abstract
Recent studies demonstrated that the angiotensin type 2 receptor (AT2R) agonist, compound 21 (C21), provides neuroprotection and enhances recovery in experimental stroke. However, C21 has never been tested in traumatic brain injury (TBI). Here, we aim to examine whether C21 confers protection after TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. C21 (0.03 mg/kg, i.p.) was administered at 1 h and 3 h post-TBI. After neurological severity score (NSS) assessments, all animals were sacrificed for immunoblotting analysis at 24 h post-TBI. C21 treatment significantly ameliorated NSS and reduced TBI’s biomarkers [high mobility group box 1 (HMGB1), aquaporin-4 (AQ4)] and inflammatory markers [interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)] in the pericontusional areas compared to saline TBI. Further, C21 treatment induced interleukin-10 (IL-10) and phosphorylation of endothelial nitric oxide synthase (eNOS) after TBI. C21 also attenuated pro-apoptotic activation of poly (ADP-ribose) polymerase (PARP) and caspase-3. These findings support the therapeutic potential of C21 against TBI.
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Acknowledgements
The authors are thankful to Dr. Anton J. Reiner for providing controlled cortical impact (CCI) device (Impact One, Leica Biosystems, Buffalo Grove, IL 60089 US) to induce TBI in mice.
Funding
This work was supported by the National Institute of Health [Grant No. R01-NS097800 (TI)].
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Study design: TI. Study conduct and data collection: SI. Approving final version of manuscript: all authors.
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Ismael, S., Ishrat, T. Compound 21, a Direct AT2R Agonist, Induces IL-10 and Inhibits Inflammation in Mice Following Traumatic Brain Injury. Neuromol Med 24, 274–278 (2022). https://doi.org/10.1007/s12017-021-08687-7
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DOI: https://doi.org/10.1007/s12017-021-08687-7