Mild traumatic brain injury induced by primary blast overpressure produces dynamic regional changes in [18F]FDG uptake

Jaiswal, Shalini; Knutsen, Andrew K.; Wilson, Charles Branch; Fu, Amanda H.; Tucker, Laura B.; Kim, Yeonho; Bittner, Katie C.; Whiting, Mark D.; McCabe, Joseph T.; Dardzinski, Bernard J.

doi:10.1016/j.brainres.2019.146400

Cited by 12 publications

(11 citation statements)

References 45 publications

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“…However, in this study, no significant changes were found in the hippocampus on 18 F-FDG PET, MRS, and immunohistochemistry from the hyperacute phase to the subacute phase. Consistent with our study, Jaiswal et al (2019) showed no significant difference between the blast-induced mTBI group and the sham group in the hippocampus on 18 F-FDG PET imaging at the acute and subacute stages. Walls et al (2016) also showed no BBB damage and colocalized neuroinflammatory changes in the hippocampus from 4 h to several days post-injury in the blast-induced TBI model.…”

Section: Discussionsupporting

confidence: 91%

“…Increased 18 F-FDG uptake in the whole brain, especially regions associated with executive and vestibulomotor function, on 1 day post-injury was reported, and then resolved by 9 days following blast to head (Awwad et al, 2015). Jaiswal et al (2019) examined 18 F-FDG uptake in the brain by VOI-and voxel-based analysis following a single blast. Like us, they observed an acute increase in 18 F-FDG uptake in the amygdala and somatosensory cortex and a decrease in multiple midbrain structures at 1-3 h following blast.…”

Section: Discussionmentioning

confidence: 99%

“…Several advanced in vivo imaging techniques have been used to investigate TBI to better understand the temporal microstructural and functional changes following TBI, such as diffusion tensor imaging (DTI), functional MRI (fMRI), MR spectroscopy (MRS), positron emission tomography (PET), etc. (Croall et al, 2014;Zhuo et al, 2015;Harris et al, 2016;Jaiswal et al, 2019;Kulkarni et al, 2019;Venkatasubramanian et al, 2020). DTI has been widely used to investigate the microstructural responses after mTBI.…”

mentioning

confidence: 99%

“…Cerebral glucose metabolism significantly associates with neuronal function and activity of the injured brain (Garnett et al, 2001;Casey et al, 2008). Clinical and animal studies have shown that changes in glucose metabolism of the brain in hours to days following exposure to blast injury have been more complex than the chronic hypometabolism using 18 F-FDG PET (Stocker et al, 2014;Awwad et al, 2015;Meabon et al, 2016;Jaiswal et al, 2019). PET imaging provides exquisite sensitivity when compared with CT or MR imaging, but with reduced resolution.…”

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confidence: 99%

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18F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats

Liu

et al. 2021

Front. Neurosci.

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A majority of blast-induced mild traumatic brain injury (mTBI) patients experience persistent neurological dysfunction with no findings on conventional structural MR imaging. It is urgent to develop advanced imaging modalities to detect and understand the pathophysiology of blast-induced mTBI. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) could detect neuronal function and activity of the injured brain, while MR spectroscopy provides complementary information and assesses metabolic irregularities following injury. This study aims to investigate the effectiveness of combining 18F-FDG PET with MR spectroscopy to evaluate acute and subacute metabolic cerebral alterations caused by blast-induced mTBI. Thirty-two adult male Sprague–Dawley rats were exposed to a single blast (mTBI group) and 32 rats were not exposed to the blast (sham group), followed by 18F-FDG PET, MRI, and histological evaluation at baseline, 1–3 h, 1 day, and 7 days post-injury in three separate cohorts. 18F-FDG uptake showed a transient increase in the amygdala and somatosensory cortex, followed by a gradual return to baseline from day 1 to 7 days post-injury and a continuous rise in the motor cortex. In contrast, decreased 18F-FDG uptake was seen in the midbrain structures (inferior and superior colliculus). Analysis of MR spectroscopy showed that inflammation marker myo-inositol (Ins), oxidative stress marker glutamine + glutamate (Glx), and hypoxia marker lactate (Lac) levels markedly elevated over time in the somatosensory cortex, while the major osmolyte taurine (Tau) level immediately increased at 1–3 h and 1 day, and then returned to sham level on 7 days post-injury, which could be due to the disruption of the blood–brain barrier. Increased 18F-FDG uptake and elevated Ins and Glx levels over time were confirmed by histology analysis which showed increased microglial activation and gliosis in the frontal cortex. These results suggest that 18F-FDG PET and MR spectroscopy can be used together to reflect more comprehensive neuropathological alterations in vivo, which could improve our understanding of the complex alterations in the brain after blast-induced mTBI.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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18F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats

Liu

et al. 2021

Front. Neurosci.

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“…Previously, we reported increased neuropathology in the somatosensory cortex and thalamus following dTBI, which could also alter sensory input into the BLA (Lisembee and Lifshitz, 2008;Thomas et al, 2018). Recent publications have also indicated subacute metabolic, and chronic metabolic and structural changes mapped directly to the CeA, and impairments in extinction of contextual fear differences at a chronic time point after experimental TBI (Zhao et al, 2018;Jaiswal et al, 2019;Kulkarni et al, 2019). In accordance with the data in this manuscript, these reports specifically identify the CeA as a vulnerable anatomic locus for future investigations, where FDA approved drugs with affinities for identified targets can be evaluated for new indications on their influence on glutamate signaling in anxiety-like behavior.…”

Section: Discussionmentioning

confidence: 95%

Experimental Traumatic Brain Injury Induces Chronic Glutamatergic Dysfunction in Amygdala Circuitry Known to Regulate Anxiety-Like Behavior

et al. 2020

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Up to 50% of traumatic brain injury (TBI) survivors demonstrate persisting and late-onset anxiety disorders indicative of limbic system dysregulation, yet the pathophysiology underlying the symptoms is unclear. We hypothesize that the development of TBIinduced anxiety-like behavior in an experimental model of TBI is mediated by changes in glutamate neurotransmission within the amygdala. Adult, male Sprague-Dawley rats underwent midline fluid percussion injury or sham surgery. Anxiety-like behavior was assessed at 7 and 28 days post-injury (DPI) followed by assessment of real-time glutamate neurotransmission in the basolateral amygdala (BLA) and central nucleus of the amygdala (CeA) using glutamate-selective microelectrode arrays. The expression of anxiety-like behavior at 28 DPI coincided with decreased evoked glutamate release and slower glutamate clearance in the CeA, not BLA. Numerous factors contribute to the changes in glutamate neurotransmission over time. In two additional animal cohorts, protein levels of glutamatergic transporters (Glt-1 and GLAST) and presynaptic modulators of glutamate release (mGluR2, TrkB, BDNF, and glucocorticoid receptors) were quantified using automated capillary western techniques at 28 DPI. Astrocytosis and microglial activation have been shown to drive maladaptive glutamate signaling and were histologically assessed over 28 DPI. Alterations in glutamate neurotransmission could not be explained by changes in protein levels for glutamate transporters, mGluR2 receptors, astrocytosis, and microglial activation. Presynaptic modulators, BDNF and TrkB, were significantly decreased at 28 DPI in the amygdala. Dysfunction in presynaptic regulation of glutamate neurotransmission may contribute to anxiety-related behavior and serve as a therapeutic target to improve circuit function.

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Persistent hypersomnia following repetitive mild experimental traumatic brain injury: Roles of chronic stress and sex differences

Portillo

Kim

et al. 2023

J of Neuroscience Research

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Traumatic brain injury (TBI) is often more complicated than a single head injury. An extreme example of this point may be military service members who experience a spectrum of exposures over a prolonged period under stressful conditions. Understanding the effects of complex exposures can inform evaluation and care to prevent persistent symptoms. We designed a longitudinal series of non-invasive procedures in adult mice to evaluate the effects of prolonged mild stress and head injury exposures. We assessed anxiety, depression, and sleep-wake dysfunction as symptoms that impact long-term outcomes after mild TBI. Unpredictable chronic mild stress (UCMS) was generated from a varied sequence of environmental stressors distributed within each of 21 days. Subsequently, mice received a mild blast combined with closed-head mild TBI on 5 days at 24-h intervals. In males and females, UCMS induced anxiety without depressive behavior. A major finding was reproducible sleep-wake dysfunction through 6-to 12-month time points in male mice that received UCMS with repetitive blast plus TBI events, or surprisingly after just UCMS alone. Specifically, male mice exhibited hypersomnia with increased sleep during the active/dark phase and fragmentation of longer wake bouts. Sleep-wake dysfunction was not found with TBI events alone, and hypersomnia was not found in females under any conditions. These results identify prolonged stress and sex differences as important considerations for sleep-wake dysfunction. Furthermore, this reproducible hypersomnia with impaired wakefulness is similar to the excessive daytime sleepiness reported in patients, including patients with TBI, which warrants further clinical screening, care, and treatment development.

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Mild traumatic brain injury induced by primary blast overpressure produces dynamic regional changes in [18F]FDG uptake

Cited by 12 publications

References 45 publications

18F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats

18F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats

Experimental Traumatic Brain Injury Induces Chronic Glutamatergic Dysfunction in Amygdala Circuitry Known to Regulate Anxiety-Like Behavior

Persistent hypersomnia following repetitive mild experimental traumatic brain injury: Roles of chronic stress and sex differences

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