Suchan Liao1,2,3, Ying Luo1,2,3, Titikorn Chunchai1,2, Kodchanan Singhanat1,2,3, Busarin Arunsak1,2, Juthipong Benjanuwattra1,2, Nattayaporn Apaijai1,2,3, Nipon Chattipakorn1,2,3, Siriporn C Chattipakorn4,5,6. 1. Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. 2. Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand. 3. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. 4. Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. siriporn.c@cmu.ac.th. 5. Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand. siriporn.c@cmu.ac.th. 6. Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand. siriporn.c@cmu.ac.th.
Abstract
OBJECTIVE: Microglial hyperactivation and apoptosis were observed following myocardial infarction and ischemia reperfusion (I/R) injury. This study aimed to test the hypothesis that the apoptosis inhibitor, Z-VAD, attenuates microglial and astrocytic hyperactivation and brain inflammation in rats with cardiac I/R injury. MATERIALS AND METHODS: Rats were subjected to either sham or cardiac I/R operation (30 min-ischemia followed by 120-min reperfusion), rats in the cardiac I/R group were given either normal saline solution or Z-VAD at 3.3 mg/kg via intravenous injection 15 min prior to cardiac ischemia. Left ventricular ejection fraction (% LVEF) was determined during the cardiac I/R protocol. The brain tissues were removed and used to determine brain apoptosis, brain inflammation, microglial and astrocyte morphology. RESULTS: Cardiac dysfunction was observed in rats with cardiac I/R injury as indicated by decreased %LVEF. In the brain, we found brain apoptosis, brain inflammation, microglia hyperactivation, and reactive astrogliosis occurred following cardiac I/R injury. Pretreatment with Z-VAD effectively increased %LVEF, reduced brain apoptosis, attenuated brain inflammation by decreasing IL-1β mRNA levels, suppressed microglial and astrocytic hyperactivation and proliferation after cardiac I/R injury. CONCLUSION: Z-VAD exerts neuroprotective effects against cardiac I/R injury not only targeting apoptosis but also microglial and astrocyte activation.
OBJECTIVE: Microglial hyperactivation and apoptosis were observed following myocardial infarction and ischemia reperfusion (I/R) injury. This study aimed to test the hypothesis that the apoptosis inhibitor, Z-VAD, attenuates microglial and astrocytic hyperactivation and brain inflammation in rats with cardiac I/R injury. MATERIALS AND METHODS: Rats were subjected to either sham or cardiac I/R operation (30 min-ischemia followed by 120-min reperfusion), rats in the cardiac I/R group were given either normal saline solution or Z-VAD at 3.3 mg/kg via intravenous injection 15 min prior to cardiac ischemia. Left ventricular ejection fraction (% LVEF) was determined during the cardiac I/R protocol. The brain tissues were removed and used to determine brain apoptosis, brain inflammation, microglial and astrocyte morphology. RESULTS: Cardiac dysfunction was observed in rats with cardiac I/R injury as indicated by decreased %LVEF. In the brain, we found brain apoptosis, brain inflammation, microglia hyperactivation, and reactive astrogliosis occurred following cardiac I/R injury. Pretreatment with Z-VAD effectively increased %LVEF, reduced brain apoptosis, attenuated brain inflammation by decreasing IL-1β mRNA levels, suppressed microglial and astrocytic hyperactivation and proliferation after cardiac I/R injury. CONCLUSION: Z-VAD exerts neuroprotective effects against cardiac I/R injury not only targeting apoptosis but also microglial and astrocyte activation.
Authors: Alice K Jacobs; Elliott M Antman; Gray Ellrodt; David P Faxon; Tammy Gregory; George A Mensah; Peter Moyer; Joseph Ornato; Eric D Peterson; Larry Sadwin; Sidney C Smith Journal: Circulation Date: 2006-03-28 Impact factor: 29.690
Authors: Max Rudolph; Christian W Schmeer; Madlen Günther; Florus Woitke; Carolin Kathner-Schaffert; Lina Karapetow; Julia Lindner; Thomas Lehmann; Gustav Jirikowski; Otto W Witte; Christoph Redecker; Silke Keiner Journal: Glia Date: 2021-05-04 Impact factor: 7.452