Mild Traumatic Brain Injury Results in Depressed Cerebral Glucose Uptake: An ¹⁸FDG PET Study

Abstract

Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

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

“…Sample sizes were calculated based on our previous work[5]. One rat was removed from the injured group due to baseline FDG measures more than 2 SD away from the mean (final n = 5).…”

“…Following brain injury, glucose uptake and metabolism have been shown to follow a pattern of elevation in the first few minutes to hours followed by sub-acute to chronic depression and slow return to baseline [5]. The glucose uptake and metabolism pattern that occurs after SCI is less well known.…”

“…We have previously demonstrated that FDG-PET is effective in detecting reductions in glucose uptake after mild traumatic brain injury and correlated this reduction with both cellular and functional alterations[5]. However, to date, only one study, published by Tewarie et al in 2010, has utilized FDG-PET after severe contusion SCI in rodents, finding significantly increased uptake surrounding the lesion peaking at 7 days post-injury (dpi)[9].…”

Current Therapeutic Modalities, Enzyme Kinetics, and Redox Proteomics in Traumatic Brain Injury

“…In order to determine the efficiency and safety of future human TBI treatment for restoration of axonal damage, recently rat models have been used as a preliminary study for stem cell treatment for TBI [4]. While understanding axonal damage is important when researching TBI, metabolic rat model studies are exploring cerebral glucose uptake in TBI metabolic pathways [5]. Results show that a decrease in cerebral glucose uptake occurs in TBI rat models with axonal damage and glial activation [5].…”

“…While understanding axonal damage is important when researching TBI, metabolic rat model studies are exploring cerebral glucose uptake in TBI metabolic pathways [5]. Results show that a decrease in cerebral glucose uptake occurs in TBI rat models with axonal damage and glial activation [5]. Therefore, glucose is unable to be transported out of the cell for use as fuel to the body, much like insulin resistance in Type-2 diabetes.…”