The Neuroprotective Effects and Probable Mechanisms of Everolimus in a Rat Model of Intracerebral Hemorrhage

In this study, a selective mTOR inhibitor, everolimus, was applied to investigate the outcome after ICH and the possible underlying mechanism. The ICH model was established by autologous blood injection. Everolimus (50 and 100 µg/kg) was administered intraperitoneally for 14 consecutive days' post-operation. The neurological functions were examined at 3, 7, and 14 days' post-ICH. Samples of brain tissue were collected to perform histopathological and immunohistochemical (NF-k-positive cell) examinations. Besides, the striatum was used to evaluate parameters related to oxidative stress (superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol levels) and inflammation markers (TNF-α and NO). Everolimus ameliorated ICH-induced neurological deficits. In addition, treatment with everolimus reduced infarct volume and NF-k-β positive cells as compared to the ICH group. Furthermore, everolimus significantly increased total thiol content and SOD activity while significantly reducing MDA, NO, and TNF- levels as compared to the ICH group. Collectively, our investigation showed that everolimus improves ICH outcome and modulates oxidative stress and inflammation after ICH. Treatment with rapamycin reduced neurological deficient, oxidative stress, and inflammation in a rat model of intracerebral hemorrhage.PMID:37747596 | DOI:10.1007/s10571-023-01409-6
Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Source Type: research