Cerebral glucose uptake is altered after repeated concussion with or without polytrauma

Objectives: Both clinical and preclinical studies have shown that repeated concussion alters brain glucose metabolism. However, the effect of polytrauma, often associated with concussion, has not been explored fully. The purpose of this study was to comprehensively characterize injury-induced changes using FDG-PET imaging following repeated closed head concussions, with or without hypoxemia and hemorrhagic shock.

Methods: Adult male Sprague-Dawley rats used in this study were divided randomly into 4 groups (12 animals/group) - repeat Sham (rSham), repeat concussion (RC), hypoxemia and hemorrhagic shock (HH) and repeat concussion with hypoxemia and hemorrhagic shock (RC+HH). The PET/CT images were acquired at three time points - prior to injury (baseline), one day post injury (D1), and seven days post injury (D7). Repeat concussions were induced using the WRAIR Projectile Concussive Impact (PCI) model (3 hits at 5 minute interval). The polytrauma procedure included hypoxemia (10% inspired oxygen) for 60 minutes and hemorrhagic shock (pressure-controlled tail artery bleeding, mean arterial pressure maintained at 30-45 mmHg) for 60 minutes. Fluid resuscitation (Lactated Ringer’s) was provided following hemorrhagic shock. Data processing and analysis of the FDG-PET data were performed using the Statistical Parametric Mapping method (SPM12, Wellcome Trust). An uncorrected p-value of 0.001 and voxel extent of 1000 voxels was used to determine cluster significance.

Results: Changes in regional brain glucose metabolism were detected between all groups (RC, HH, and RC+HH compared to Sham) at D1 post injury. In the HH group, significantly increased uptake was observed in a region centered on the mammillary bodies (p = 0.005 at cluster level; p < 0.001 at peak level) while decreased uptake was observed in multiple regions of primary somatosensory cortex (p = 0.026 and 0.043 at cluster level; p = 0.031 at peak level). In the RC group, significantly increased uptake was observed in the caudate putamen relative to shams (p = 0.031 at cluster level; p = 0.003 at peak level). In the combined HH+RC group, significantly increased uptake was observed in multiple regions including olfactory bulb (p < 0.001 at cluster level and peak level), internal capsule (p = 0.007 at peak level) and medial entorhinal cortex (p = 0.019 at peak level), while significantly decreased uptake was observed in primary somatosensory (p < 0.002 at both cluster and peak level) and retrosplenial cortex (p = 0.003 at peak level). By D7, no significant differences were observed between RC, HH, and RC+HH groups compared to sham. Table 1 (supplemental data) summarizes the brain regions with significant clusters or peaks of altered glucose metabolism by group.

Conclusions: HH, RC, and RC+HH alter glucose metabolism, which can be detected with FDG-PET imaging acutely following injury; however, by D7, no changes were detected. These data indicate that early PET imaging is capable of detecting acute transient changes in brain glucose metabolism following repeat concussion, with or without combined polytrauma. References: 1. Leung et. al. Front Neurol. 2018 Aug 3; 9:612 2. Leung et. al. Ann Biomed Eng. 2014 Aug; 42(8): 1618-30 3. Divani et. al. J Neurotrauma 2018 Jan 1; 35(1): 187-194 4. Selwyn et. al. J Neurotrauma 2016 Aug 15; 33(16): 1479-91 5. Vallez Garcia et. al. J Neurotrauma 2016 Oct 15; 33(20): 1855-1865