18F-FDG-PET imaging of rat spinal cord demonstrates altered glucose uptake acutely after contusion injury

Abstract

Spinal cord injury (SCI) results in an acute reduction in neuronal and glial cell viability, disruption in axonal tract integrity, and prolonged increases in glial activity and inflammation, all of which can influence regional metabolism and glucose utilization. To date, the understanding of glucose uptake and utilization in the injured spinal cord is limited. Positron emission tomography (PET)-based measurements of glucose uptake may therefore serve as a novel bio-marker for SCI. This study aimed to determine the acute and sub-acute glucose uptake pattern after SCI to determine its potential as a novel non-invasive tool for injury assessment and to begin to understand the glucose uptake pattern following acute SCI. Briefly, adult male Sprague-Dawley rats were subjected to moderate contusion SCI, confirmed by locomotor function and histology. PET imaging with [18F]Fluorodeoxyglucose (FDG) was performed prior to injury and at 6 and 24 hours and 15 days post-injury (dpi). FDG-PET imaging revealed significantly depressed glucose uptake at 6 hours post-injury at the lesion epicenter that returned to sham/naïve levels at 24 hours and 15 dpi after moderate injury. FDG uptake at 15 dpi was likely influenced by a combination of elevated glial presence and reduced neuronal viability. These results show that moderate SCI results in acute depression in glucose uptake followed by an increase in glucose uptake that may be related to neuroinflammation. This acute and sub-acute uptake, which is dependent on cellular responses, may represent a therapeutic target.

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

“…These changes were observed in both white and gray matter at the lesion site (Schechter et al, 1990). In a rat model of moderate contusion SCI, we have found that injury resulted in a marked reduction in glucose uptake at 6 h post-injury, as measured by FDG-PET imaging (von Leden et al, 2016). This glucose uptake depression then returned to baseline levels and remained there throughout the following 2 weeks of the study, although other studies have suggested that the uptake of FDG increases after the first 24 h, to peak at 7 days post-injury (Nandoe Tewarie et al, 2010).…”

“…In addition, we demonstrated that these changes in glucose uptake were dependent on subject age. Increasing the age of rats from 3 months (von Leden et al, 2016) to 12 months (von Leden et al, 2019) resulted in a significant alteration in the glucose uptake profile. Aged rats showed no significant change in glucose uptake acutely after injury, but did show a marked increase in glucose uptake by 14 days post-injury (von Leden et al, 2019).…”

Zinc Regulates Glucose Metabolism of the Spinal Cord and Neurons and Promotes Functional Recovery after Spinal Cord Injury through the AMPK Signaling Pathway

“…Studies have shown that energy fluctuations caused by changes in glucose uptake are closely linked to the survival of the neurons [ 5 , 9 ]. After SCI, the glucose uptake of the spinal cord of rodents was decreased, with the metabolism disturbance, and neuronal activity was inhibited [ 32 ]. The entry of glucose into cells depends on glucose transporters.…”

Wireless Epidural Electrical Stimulation in Combination With Serotonin Agonists Improves Intraspinal Metabolism in Spinal Cord Injury Rats

“…In order to normalize the primary SUV to the relative SUV (SUVR), the cerebellum and baseline in its resting state after SCI for a week were used as the reference (31,32). The SUVR was expressed as the average of three SUVRs by repeating the measurement three times.…”

“…The main mechanism underlying this phenomenon is that electrical stimulation induces vasodilation via the release of vasoactive neuropeptides such as calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide in the dura mater, increasing blood supply to the stimulated area (50,51). Nevertheless, it is not clear why WEES alone cannot increase task metabolism compared with its matched basal metabolism; however, this is likely because hemodynamic response and glucose uptake involve different processes (16,31,52). While WEES alone increased the blood supply, the WEES-induced locomotor intensity was relatively low and could not therefore fully stimulate the spinal cord neural cells to uptake proportionally matched glucose.…”