Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative
- PDF / 2,932,976 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 99 Downloads / 178 Views
www.neurosci.cn www.springer.com/12264
ORIGINAL ARTICLE
Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice Xun Wu1 • Wenxing Cui1 • Wei Guo1 • Haixiao Liu1 • Jianing Luo1 • Lei Zhao1 Hao Guo1 • Longlong Zheng1 • Hao Bai1 • Dayun Feng1 • Yan Qu1
•
Received: 10 November 2019 / Accepted: 21 January 2020 Ó The Author(s) 2020
Abstract Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynaminrelated protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we Xun Wu, Wenxing Cui and Wei Guo have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00505-7) contains supplementary material, which is available to authorized users. & Dayun Feng [email protected] & Yan Qu [email protected] 1
Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China
uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acroleininduced brain injury. Keywords Intracerebral hemorrhage Secondary brain injury Acrolein Drp1 Mitochondrial oxidative damage
Introduction Intracerebral hemorrhage (ICH) is an acute cerebrovascular event with a high mortality and disability rate [1, 2]. Pathological processes after ICH include not only primary brain injury, but also secondary brain injury (SBI) [3, 4]. Primary brain injury refers to the physical disruption of the cellular architecture induced by the initial hematoma. Meanwhile, the hematoma leads to SBI, which includes oxidative damage, the inflammatory response, glutamate toxicity, neural death, and blood-brain barrier disruption [5–7]. Strategies targeting SBI are of great importance for both experimental and clinical studies. Although multiple treatments have emerged in clinical practice, the outcomes of ICH remain unsatisfactory [8]. These considerations
Data Loading...
