Abstract
PurposeThe mammalian brain glucose metabolism is tightly and sensitively regulated. An ischemic brain injury caused by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) affects cerebral function and presumably also glucose metabolism. The majority of patients who survive CA suffer from cognitive deficits and physical disabilities. Toll-like receptor 2 (TLR2) plays a crucial role in inflammatory response in ischemia and reperfusion (I/R). Since deficiency of TLR2 was associated with increased survival after CA-CPR, in this study, glucose metabolism was measured using non-invasive [18F]F-FDG PET-CT imaging before and early after CA-CPR in a mouse model comparing wild-type (WT) and TLR2-deficient (TLR2−/−) mice. The investigation will evaluate whether FDG-PET could be useful as an additional methodology in assessing prognosis.ProceduresTwo PET-CT scans using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) tracer were carried out to measure dynamic glucose metabolism before and early after CPR. To achieve this, anesthetized and ventilated adult female WT and TLR2−/− mice were scanned in PET-CT. After recovery from the baseline scan, the same animals underwent 10-min KCL-induced CA followed by CPR. Approximately 90 min after CA, measurements of [18F]F-FDG uptake for 60 min were started. The [18F]F-FDG standardized uptake values (SUVs) were calculated using PMOD-Software on fused FDG-PET-CT images with the included 3D Mirrione-Mouse-Brain-Atlas.ResultsThe absolute SUVmean of glucose in the whole brain of WT mice was increased about 25.6% after CA-CPR. In contrast, the absolute glucose SUV in the whole brain of TLR2−/− mice was not significantly different between baseline and measurements post CA-CPR. In comparison, baseline measurements of both mouse strains show a highly significant difference with regard to the absolute glucose SUV in the whole brain. Values of TLR2−/− mice revealed a 34.6% higher glucose uptake.ConclusionsThe altered mouse strains presented a different pattern in glucose uptake under normal and ischemic conditions, whereby the post-ischemic differences in glucose metabolism were associated with the function of key immune factor TLR2. There is evidence for using early FDG-PET-CT as an additional diagnostic tool after resuscitation. Further studies are needed to use PET-CT in predicting neurological outcomes.
Highlights
Out-of-hospital cardiac arrest (CA) strikes every year about 95.9/100,000 adults worldwide [1]
No difference appeared in the kinetics of exponential glucose uptake in baseline PET scans over time among the mouse strains seen by a strong positive correlation (WT vs. T LR2−/−, R = 0.969)
The analysis of correlation shows that glucose uptake followed very similar kinetics over time in investigated groups and baseline and PET scans post CA-cardiopulmonary resuscitation (CPR)
Summary
Out-of-hospital cardiac arrest (CA) strikes every year about 95.9/100,000 adults worldwide [1]. Cardiopulmonary resuscitation (CPR) and return of spontaneous circulation (ROSC) lead to cerebral reperfusion and oxygenation, a further consequence is a severe ischemia–reperfusion (I/R) injury leading to an excessive systemic inflammatory response, often called postcardiac arrest syndrome [8,9,10]. Cerebral inflammation is characterized by activation of glial cells, an influx of peripheral immune and inflammatory cells, high concentrations of reactive oxygen species (ROS), and release of pro-inflammatory mediators such as cytokines and adhesion molecules [11,12,13,14]. TLR2-deficient (TLR2−/−) individuals showed lower release of pro-inflammatory cytokines, which improved survival after CA-CPR in the mouse model [24]
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