Abstract 19227: In-vivo Pet Imaging of Long-Term Microglia-Activation After Cardiac Arrest in Rats
Objective: Half of the survivors of cardiac arrest (CA) suffer from permanent impairment of cognitive functions. CA is a state of global cerebral ischaemia that causes delayed neuronal death in selectively vulnerable brain areas including the hippocampus within the first seven days after the collapse. Subsequently, the resident macrophage cells of the brain known as microglia are being activated. Studies involving animals with focal cerebral ischaemia suggest that those microglial cells can mediate the destruction of neurons and may facilitate dementia years after being activated. However, chronic secondary events after CA, such as microglia activation still remain unclear. Therefore, the objective was to precisely locate potentially activated microglial cells by use of positron-emission-tomography [PET] within six months after CA.
Methods: Cardiopulmonary resuscitation (CPR) was performed six minutes after induction of ventricular fibrillation in narcotized Wistar rats (intervention group: n=5 animals). The algorithm included external chest compressions (200/min), administration of adrenaline (20 μg/kg) and sodium bicarbonate and defibrillations with 2-3J. n=3 animals served as controls. Animals underwent PET-measurements at day 5, 8, 13, 90, and 180 after CA. For PET-measurements of activated microglia cells, the “translocator-protein”-ligand [18F]DAA1106 was used. Images were co-registered to an MRI template, smoothed with a Gauss kernel (1.5 mm full width at half maximum), and image intensity was normalized to cerebral background. “Standardized uptake value ratios” (SUVRs) were extracted from striatal and hippocampal “volumes of interest” (VOI). At day 140 after CA, T2-weighted structural MR imaging was conducted.
Results: Activated microglia cells were detected in the dorsal hippocampus (n=5) and in the striatum (n=2) at day 180 after CA. [18F]DAA1106 binding remained constant over 180 days and was associated with structural changes, i.e. hypointensities in the striatum and tissue atrophy in the hippocampus.
Conclusion: Long-term microglia activation was apparent 6 months after CA in rats. Conjunction with the appearance of dementia as late sequela of CA could not be excluded and needs to be examined in further studies.
Author Disclosures: D. de la Puente Bethencourt: None. D.C. Schroeder: None. E. Popp: None. J. Zischler: None. T. Annecke: None. T. Hucho: None. B. Neumaier: None. B.W. Böttiger: None. H. Endepols: None.
- © 2016 by American Heart Association, Inc.