Previous attempts to identify neuroprotective targets for acute ischemic stroke by studying ischemic cascades and devising ways to suppress these pathways have failed in translational research. We hypothesized that studying the molecular determinants of endogenous neuroprotection, namely, the tolerance against ischemic stroke conferred by hyperbaric oxygen (HBO) preconditioning, via a well-established paradigm would reveal new neuroprotective targets. By a combination of proteomics, KEGG pathway analysis, lysosome fraction and western blot analysis, we found that chaperone-mediated autophagy (CMA) was activated by HBO preconditioning. In addition, LAMP2A is uniquely decreased in cortical neurons in the early stage of stroke. Suppression of CMA with recombinant adeno-associated viral vector (rAAV)-mediated delivery of short hairpin RNAs (shRNAs) targeting the LAMP2A transcript increased the neuronal susceptibility of apoptosis and abolished the neuroprotection induced by HBO preconditioning. Administration of the clinically utilized FDA-approved drug mycophenolate mofetil induced long-term neuroprotection post-stroke in a CMA-dependent manner. In summary, HBO preconditioning confers neuroprotection against ischemia by inducing CMA, which is a promising translational treatment target for stroke.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.brainres.2024.149315 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chaperone-mediated autophagy (CMA) confers neuroprotection of HBO preconditioning against stroke.
Brain Res
January 2025
Department of Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, Shaanxi, PR China; Department of Critical Care Medicine, Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, PR China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, PR China. Electronic address:
Previous attempts to identify neuroprotective targets for acute ischemic stroke by studying ischemic cascades and devising ways to suppress these pathways have failed in translational research. We hypothesized that studying the molecular determinants of endogenous neuroprotection, namely, the tolerance against ischemic stroke conferred by hyperbaric oxygen (HBO) preconditioning, via a well-established paradigm would reveal new neuroprotective targets. By a combination of proteomics, KEGG pathway analysis, lysosome fraction and western blot analysis, we found that chaperone-mediated autophagy (CMA) was activated by HBO preconditioning.
View Article and Find Full Text PDFHyperbaric oxygen preconditioning rescues prolonged underwater exercise-induced hippocampal dysfunction by regulating microglia activation and polarization.
Neurosci Res
October 2024
Department of Diving and Hyperbaric Medicine, Navy Special Medical Center, Naval Medical University, Shanghai 200433, China. Electronic address:
Underwater exercise is becoming increasingly prevalent, during which brain function is necessary but is also at risk. However, no study has explored how prolonged exercise affect the brain in underwater environment. Previous studies have indicated that excessive exercise in common environment causes brain dysfunction but have failed to provide appropriate interventions.
View Article and Find Full Text PDFEffects of remote ischemic preconditioning on early markers of intestinal injury in experimental hemorrhage in rats.
Sci Rep
June 2024
Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany.
The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging.
View Article and Find Full Text PDFHyperbaric Oxygen Reduces Oxidative Stress Impairment and DNA Damage and Simultaneously Increases HIF-1α in Ischemia-Reperfusion Acute Kidney Injury.
Int J Mol Sci
March 2024
Department of Cardiovascular Physiology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI.
View Article and Find Full Text PDFHyperbaric Oxygen Upregulates Mst1 to Activate Keap1/Nrf2/HO-1 Pathway Resisting Oxidative Stress in a Rat Model of Acute Myocardial Infarction.
Mol Biotechnol
January 2025
Emergency Department, Affiliated Hospital of Hebei Engineering University, Congtai District, No. 81, Congtai Road, Handan, 056008, Hebei, China.
This study aimed to investigate the protective effects and mechanisms of hyperbaric oxygen (HBO) preconditioning in a rat model of acute myocardial infarction (MI) established by ligation of the left anterior descending (LAD) coronary artery. Microarray, real-time PCR, and western blotting (WB) results demonstrated that the Mst1 gene was downregulated in the heart tissue of the MI rat model. HBO preconditioning significantly increased Mst1 expression in cardiac tissues of rats after MI modeling.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!