AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice
Issued Date
2022-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85136210706
Pubmed ID
35995819
Journal Title
Scientific Reports
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.12 No.1 (2022)
Suggested Citation
Timaru-Kast R., Garcia Bardon A., Luh C., Coronel-Castello S.P., Songarj P., Griemert E.V., Krämer T.J., Sebastiani A., Steckelings U.M., Thal S.C. AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice. Scientific Reports Vol.12 No.1 (2022). doi:10.1038/s41598-022-18338-x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86399
Title
AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice
Other Contributor(s)
Abstract
Antagonism of the angiotensin II type 1 receptor (AT1) improves neurological function and reduces brain damage after experimental traumatic brain injury (TBI), which may be partly a result of enhanced indirect angiotensin II type 2 receptor (AT2) stimulation. AT2 stimulation was demonstrated to be neuroprotective via anti-inflammatory, vasodilatory, and neuroregenerative mechanisms in experimental cerebral pathology models. We recently demonstrated an upregulation of AT2 after TBI suggesting a protective mechanism. The present study investigated the effect of post-traumatic (5 days after TBI) AT2 activation via high and low doses of a selective AT2 agonist, compound 21 (C21), compared to vehicle-treated controls. No differences in the extent of the TBI-induced lesions were found between both doses of C21 and the controls. We then tested AT2-knockdown animals for secondary brain damage after experimental TBI. Lesion volume and neurological outcomes in AT2-deficient mice were similar to those in wild-type control mice at both 24 h and 5 days post-trauma. Thus, in contrast to AT1 antagonism, AT2 modulation does not influence the initial pathophysiological mechanisms of TBI in the first 5 days after the insult, indicating that AT2 plays only a minor role in the early phase following trauma-induced brain damage.