Affiliation:
1. Sichuan University West China School of Basic Medical Sciences and Forensic Medicine
2. Shanghai Jiaotong University: Shanghai Jiao Tong University
3. Sichuan University
Abstract
Abstract
Traumatic brain injury (TBI) is a significant global health issue due to its high morbidity and mortality, as well as its adverse outcomes. The resulting excessive healthcare and economic burden make it urgent to find effective drugs for TBI. Aminophylline (AMP), a classical drug widely used in the treatment of cardiovascular diseases and bronchiectasis, has recently been found to play an important role in protecting neurons in hypoxia brain injury by a variety of mechanisms. However, its therapeutic effect on TBI remains unknown. To this end, the present study aims to explore whether and how AMP improves TBI prognosis, as well as the underlying mechanisms. We found that AMP administration ameliorated neuronal ferroptosis in the cortex, improved cognitive impairment and motor dysfunction in mice following controlled cortical impact (CCI). microRNA (miRNA) profiling and related validation experiments revealed that miR-128-3p expression significantly decreased at 3h and 6h after CCI, and this change was further enhanced after AMP administration. Subsequent gain of function studies demonstrated that over-expressing miR-128-3p can aggravate neuronal ferroptosis by targeting recombinant solute carrier family 7, member 11 (Slc7a11), through which AMP exerted its therapeutic role in attenuating the cognitive impairment and motor dysfunction in mice following CCI. Overall, this study reports for the first time that AMP protects against ferroptotic neuronal death in CCI mice through miR-128-3p / Slc7a11 axis, which could be a potential treatment for TBI patients.
Publisher
Research Square Platform LLC
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