Melatonin improves neurological outcomes and preserves hippocampal mitochondrial function in a rat model of cardiac arrest

Abstract

Cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) has been implicated in the poor prognosis of CA survivors. This study was designed to evaluate the impact of melatonin on postresuscitation neurological outcomes and to explore the underlying mechanism. Sprague-Dawley rats were randomly assigned to four groups: sham group, CPR group, melatonin pretreatment group (Pre-M) and posttreatment group (Post-M). For the last 2 groups, daily melatonin gavage was performed for 12 consecutive days before or 24 hours after rat survival from CA/CPR. No statistical differences were observed in heart rate (HR), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) at baseline and after restoration of spontaneous circulation (ROSC) among groups. However, melatonin pretreatment or posttreatment significantly improved neurological deficit score and memory and spatial learning ability after CA/CPR. Further studies demonstrated that the complex I- and complex-II supported mitochondrial respiration were greatly increased under melatonin treatment. In addition, melatonin treatment preserved the mitochondrial-binding hexokinase II (HKII) and ATP levels and suppressed the upregulated protein lysine acetylation in hippocampus after CA/CPR. In conclusion, using a rat asphyxial CA model we have demonstrated that treatment with melatonin either before or after CA/CPR provides a promising neuroprotective effect, and this protection was mediated by increasing mitochondrial HKII expression, suppressing protein acetylation and improving mitochondrial function in hippocampus.

High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience

“…Bro-Jeppesen et al reported baseline plasma IL-6 and IL-10 levels were significantly higher in non-survivors compared with survivors [11,12]. Melatonin, an anti-oxidant and anti-inflammatory agent, improves neurological outcomes and preserves hippocampal mitochondrial function in cardiac arrest [36], which may be associated with its protection against inflammation [22,[37][38][39], myocardial ischemia-reperfusion injury [40][41][42][43], ventricular fibrillation [44], cardiac hypertrophy [45], dilated cardiomyopathy [46], and mitochondria-related disorders [47,48]. As neutralization of IL-17 rescues neuroinflammation [49], melatonin may contribute to the complex role of IL-17 signaling in ROSC [50].…”

Vagus Nerve Stimulation Improves Mitochondrial Dysfunction in Post–cardiac Arrest Syndrome in the Asphyxial Cardiac Arrest Model in Rats

“…Previous preclinical cardiac arrest models in rats and pigs have revealed the decreased CI and CII function in the mitochondria of hippocampus ( Yang et al, 2018 ; Lautz et al, 2019 ; Marquez et al, 2020 ). Although the global brain ischemia with reperfusion model was utilized, another study demonstrated CI suppression in mitochondria in the hippocampus and cortex during ischemia ( Chomova et al, 2012 ; Borutaite et al, 2013 ).…”

Pretreatment with human urine‑derived stem cells protects neurological function in rats following cardiopulmonary resuscitation after cardiac arrest

“…H2012043 Fresenius Kabi Deutschland GmbH) were injected via the femoral vein, and then blood pressure and heart rate were measured, and electrocardiograms were recorded. Restoration of spontaneous circulation was defined as an increase in mean arterial pressure >60 mmHg lasting ≥10 min following spontaneous rhythm ( 21 ). If spontaneous rhythm did not appear after 3 min of chest compressions or if the SBP fell <60 mmHg, rescue was abandoned, and resuscitation was considered unsuccessful.…”