Early post-ischemic glucose metabolism is dependent on function of TLR2: a study using [18F]FDG PET-CT in a mouse model of cardiac arrest and cardiopulmonary resuscitation

Abstract

Purpose: An ischemic brain injury caused by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) affects cerebral function and presumably also brain glucose metabolism. The majority of patients who survive CA suffer from cognitive deficits and physical disabilities. Toll-like receptor 2 (TLR2) plays a cruical 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]FDG PET-CT imaging before and early after CA-CPR in a mouse model comparing wild type (WT) and TLR2-deficient (TLR2-/-) mice. Methods: Two PET-CT scans using [18F]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-minute CA followed by CPR and approximately 90 min after CA measurements of [18F]FDG uptake were started. The [18F]FDG standardized uptake values (SUVs) were calculated using PMOD-Software on fused FDG-PET-CT images with the included 3D Mirrione-Mouse-Brain-Atlas. Results: The absolute SUV of glucose in the whole brain of WT mice was increased after CA-CPR. In contrast, the absolute glucose SUV in the whole brain of TLR2-/- mice was not significantly different between basal and measurements after CA-CPR. In comparison, basal measurements of both mouse strains show a significant difference in the whole brain absolute glucose SUVs, whereby TLR2-/- mice revealed 34.6% higher values. The altered mouse strains presented a different pattern in glucose uptake under normal and ischemic conditions. Conclusion: There is evidence that the post-ischemic differences in glucose metabolism were associated with the function of TLR2 and that PET-CT imaging could be useful as an additional methodology in assessing diagnosis and prognosis during post-cardiac arrest care. Further studies are needed.