Astragaloside IV ameliorates peripheral immunosuppression induced by cerebral ischemia through inhibiting HPA axis

This study investigated the effect of ASIV on cerebral ischemia-induced peripheral immunosuppression and the underlying mechanism in a mouse model of middle cerebral artery occlusion (MCAO). Our results showed that ASIV significantly prevented the atrophy of spleen and the reduction of splenic cell count. Meanwhile, ASIV preserved cell numbers of splenic NK, T, and B cells in the spleen. ASIV also suppressed apoptosis of splenic cells and preserved their proliferation ability. In addition, ASIV robustly reduced the mRNA expression of TNF-α, IL-1β, IL-6 and CRH in the hypothalamus, as well as the enlargement of adrenal gland and the increase of corticosterone in blood, indicating the inhibition of HPA axis by ASIV. Furthermore, ASIV did not enhance the effect of HPA inhibition on reducing splenic atrophy and preserving splenic NK, T, and B cell numbers in MCAO mice. Of note, ASIV did not attenuate splenic cell apoptosis induced by prednisolone, suggesting that ASIV may ameliorate splenic apoptosis through reducing peripheral glucocorticoid level. Our findings demonstrate that ASIV ameliorates post-ischemic peripheral immunosuppression through inhibiting the activation of HPA axis and targeting HPA activation to ameliorate peripheral immunosuppression may be a promising strategy to improve clinical outcomes of ischemic stroke.PMID:35091336 | DOI:10.1016/j.intimp.2022.108569
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research