scholarly journals An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging

2021 ◽  
Vol 22 (2) ◽  
pp. 951
Author(s):  
Krishna Kanta Ghosh ◽  
Parasuraman Padmanabhan ◽  
Chang-Tong Yang ◽  
Zhimin Wang ◽  
Mathangi Palanivel ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Pet Imaging ◽  
Right Hemisphere ◽  
Benzodiazepine Receptors ◽  
Translocator Protein ◽  
Molecular Alterations ◽  
Fluid Percussion ◽  
The Brain

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.

scholarly journals PET Imaging of Neurodegeneration With [18F]AV-1451 PET After Repetitive Traumatic Brain Injury

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Matthew Mesley ◽  
Ross Puffer ◽  
Charles Laymon ◽  
Brian Lopresti ◽  
Kathryn Edelman ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Pet Imaging ◽  
Neuropsychological Test ◽  
Neuropsychological Testing ◽  
Uptake Pattern ◽  
Increased Risk ◽  
History Of

Abstract INTRODUCTION TBI (traumatic brain injury) is associated with an increased risk of late neurodegeneration in chronic TBI survivors. The underlying pathophysiology of trauma-related neurodegeneration is hypothesized to involve a tauopathy, with p-tau deposited in beta-pleated sheets. Current research focuses on identifying strategies to detect trauma-related neurodegeneration in-Vivo. [F-18]AV-1451, a tau-specific PET radiotracer, may detect hyper-phosphorylated tau deposits in living patients. METHODS Participants with a history of TBI >6 mo prior with concern for cognitive decline with age-matched controls were recruited. Subjects were classified into three groups: few (=3 TBI exposures), intermediate (4–10 exposures), and numerous (>10 exposures). Participants underwent PET imaging with [F-18]AV-1451, and qualitative and semi-quantitative (SUVR) analyses of radiotracer retention were performed. Visual classification of tau positivity (+/−) was performed with absence of established positivity thresholds for [F-18]AV-1451 SUVR values. All subjects underwent neuropsychological evaluation, including measures of processing speed, executive function, and memory. RESULTS Twenty-seven TBI subjects and 7 controls were enrolled. A total of 9 participants were categorized as few, 2 as intermediate, 7 as numerous. All TBI subjects demonstrated impairment on at least one neurocognitive measure, while control subjects had normal neuropsychological test results. Analysis of [F-18]AV-1451 uptake patterns demonstrated evidence of tauopathy in 3 subjects, based on visual reads. Significantly increased [F-18]AV-1451 retention was noted in occipital gray matter, posterior cingulate gyrus, and parietal cortex in these 3 tau (+) TBI subjects compared to 24 TBI subjects visually classified as tau (−) and also normal controls. CONCLUSION Evidence of tauopathy, indicative of trauma-related neurodegeneration, was noted in 3 chronic TBI subjects, all of whom were categorized as numerous (>10) TBI exposures and cognitive deficits on neuropsychological testing. No tau PET [F-18]AV-1451 uptake was noted in control participants or in participants categorized as few or intermediate. The data represent a possible [F-18]AV-1451 PET uptake pattern associated with a clinical neurodegeneration syndrome in repetitive TBI.

scholarly journals Transcriptional Pathology Evolves Over Time in Rat Hippocampus Following Lateral Fluid Percussion Traumatic Brain Injury

2021 ◽  
Author(s):  
Rinaldo Catta-Preta ◽  
Iva Zdillar ◽  
Bradley Jenner ◽  
Emily T. Doisy ◽  
Kayleen Tercovich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Cell Death ◽  
Brain Injury ◽  
Injury Severity ◽  
Cholesterol Metabolism ◽  
Fluid Percussion ◽  
Differential Gene ◽  
Lateral Fluid Percussion ◽  
The Brain

Traumatic brain injury (TBI) causes acute and lasting impacts on the brain, driving pathology along anatomical, cellular, and behavioral dimensions. Rodent models offer the opportunity to study TBI in a controlled setting, and enable analysis of the temporal progression that occurs from injury to recovery. We applied transcriptomic and epigenomic analysis, characterize gene expression and in ipsilateral hippocampus at 1 and 14 days following moderate lateral fluid percussion (LFP) injury. This approach enabled us to identify differential gene expression (DEG) modules with distinct expression trajectories across the two time points. The major DEG modules represented genes that were up- or downregulated acutely, but largely recovered by 14 days. As expected, DEG modules with acute upregulation were associated with cell death and astrocytosis. Interestingly, acutely downregulated DEGs related to neurotransmission mostly recovered by two weeks. Upregulated DEG modules related to inflammation were not necessarily elevated acutely, but were strongly upregulated after two weeks. We identified a smaller DEG module with delayed upregulation at 14 days including genes related to cholesterol metabolism and amyloid beta clearance. Finally, differential expression was paralleled by changes in H3K4me3 at the promoters of differentially expressed genes at one day following TBI. Following TBI, changes in cell viability, function and ultimately behavior are dynamic processes. Our results show how transcriptomics in the preclinical setting has the potential to identify biomarkers for injury severity and/or recovery, to identify potential therapeutic targets, and, in the future, to evaluate efficacy of an intervention beyond measures of cell death or spatial learning.

scholarly journals Prognostic significance of translocator protein in the brain tissue following traumatic brain injury

2021 ◽  
Author(s):  
Qing Bao ◽  
Xuesong Yuan ◽  
Xiaoxing Bian ◽  
Wenfeng Wei ◽  
Peng Jin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Brain Tissue ◽  
Characteristic Curve ◽  
Prognostic Significance ◽  
Translocator Protein ◽  
Specificity And Sensitivity ◽  
Unit Increase ◽  
The Brain

Abstract Background The study aimed to measure the expression of translocator protein (TSPO) in brain tissue following traumatic brain injury (TBI) and to determine whether TSPO can predict outcomes. Methods TBI patients requiring emergent craniectomy and removing of intracranial hematoma were recruited from Wujin Hospital Affiliated with Jiangsu University between January 2018 and May 2020. TBI patients were divided into unfavorable and favorable groups according to GOS score. The TSPO in brain samples was analyzed by western blot and immunocytochemistry. Results The western blot and immunocytochemistry showed that the TSPO in the unfavorable group was higher than that in the favorable group. Double immunofluorescence staining exhibited that the percentage of TSPO positive cells in IBA1 and GFAP positive cells was 45.2 ± 3.1% and 3.5 ± 0.6% respectively. After adjusting for age, sex, CT, ICP and GCS, we found each 1-unit increase in TSPO was associated with 40% higher occurrence of unfavorable outcome (OR = 1.4, 95% CI 0.4–5.6). The area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of TSPO was 0.87, 76.7%, 88.2% respectively. Conclusion Our study demonstrated that higher TSPO was associated with higher occurrence of unfavorable outcomes.

scholarly journals PD-L1-expressing astrocytes act as a gate-keeper for neuroinflammation in the central nervous system of mice with traumatic brain injury

2021 ◽  
Author(s):  
Xiang Gao ◽  
Wei Li ◽  
Fahim Syed ◽  
Fang Yuan ◽  
Ping Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
De Novo ◽  
Gene Knockout ◽  
Reactive Astrocytes ◽  
Immune Checkpoints ◽  
Enhanced Production ◽  
The Brain

Background: Tissue damage and cellular destruction are the major events in traumatic brain injury (TBI), which trigger sterile neuroimmune and neuroinflammatory responses in the brain. While appropriate acute and transient neuroimmune and neuroinflammatory responses facilitate the repair and adaptation of injured brain tissues, prolonged and excessive neuroimmune and neuroinflammatory responses exacerbate brain damage. The mechanisms that control the intensity and duration of neuroimmune and neuroinflammatory responses in TBI largely remain elusive. Methods: We used the controlled cortical impact (CCI) model of TBI to study the role of immune checkpoints (ICPs), key regulators of immune homeostasis, in the regulation of neuroimmune and neuroinflammatory responses in the brain in vivo. Results: We found that de novo expression of PD-L1, a potent inhibitory ICP, was robustly and transiently induced in reactive astrocytes, but not in microglial cells, neurons, or oligodendrocyte progenitor cells (OPCs). These PD-L1+ reactive astrocytes were highly enriched to form a dense zone around the TBI lesion. Blockade of PD-L1 signaling enlarged brain tissue cavity size, increased infiltration of inflammatory Ly-6CHigh monocytes/macrophages (M/Mɸ) but not tissue-repairing Ly-6CLow/F4/80+ M/Mɸ, and worsened TBI outcomes in mice. PD-L1 gene knockout enhanced production of CCL2 that interacted with its cognate receptor CCR2 on Ly-6CHigh M/Mϕ to chemotactically recruit these cells into inflammatory sites. Mechanically, PD-L1 signaling in astrocytes likely exhibits dual inhibitory activities for the prevention of excessive neuroimmune and neuroinflammatory responses to TBI through (1) the PD-1/PD-L1 axis to suppress the activity of brain-infiltrating PD-1+ immune cells such as PD-1+ T cells, and (2) PD-L1 reverse signaling to regulate the timing and intensity of astrocyte reactions to TBI. Conclusions: PD-L1+ astrocytes act as a gatekeeper to the brain to control TBI-related neuroimmune and neuroinflammatory responses, thereby opening a novel avenue to study the role of ICP-neuroimmune axes in the pathophysiology of TBI and other neurological disorders.

scholarly journals Glutamate and GABA concentrations following mild traumatic brain injury: a pilot study

2018 ◽  
Vol 120 (3) ◽  
pp. 1318-1322 ◽  
Author(s):  
Alia L. Yasen ◽  
Jolinda Smith ◽  
Anita D. Christie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Primary Motor Cortex ◽  
Brain Regions ◽  
Resonance Spectroscopy ◽  
Multiple Time ◽  
Time Points ◽  
The Brain

Animal models of mild traumatic brain injury (mTBI) suggest that metabolic changes in the brain occur immediately after a mechanical injury to the head. Proton magnetic resonance spectroscopy (1H-MRS) can be used to determine relative concentrations of metabolites in vivo in the human brain. The purpose of this study was to determine concentrations of glutamate and GABA in the brain acutely after mTBI and throughout 2 mo of recovery. Concentrations of glutamate and GABA were obtained using 1H-MRS in nine individuals who had suffered an mTBI and nine control individuals in two brain regions of interest: the primary motor cortex (M1), and the dorsolateral prefrontal cortex (DLPFC), and at three different time points postinjury: 72 h, 2 wk, and 2 mo postinjury. There were no differences between groups in concentrations of glutamate or GABA, or the ratio of glutamate to GABA, in M1. In the DLPFC, glutamate concentration was lower in the mTBI group compared with controls at 72 h postinjury (d = 1.02), and GABA concentration was lower in the mTBI group at 72 h and 2 wk postinjury (d = 0.81 and d = 1.21, respectively). The ratio of glutamate to GABA in the DLPFC was higher in the mTBI group at 2 wk postinjury (d = 1.63). These results suggest that changes in glutamate and GABA concentrations in the brain may be region-specific and may depend on the amount of time that has elapsed postinjury. NEW & NOTEWORTHY To our knowledge, this is the first study to examine neurotransmitter concentrations in vivo at multiple time points throughout recovery from mild traumatic brain injury in humans.

scholarly journals Prion-Like Propagation Mechanisms in Tauopathies and Traumatic Brain Injury: Challenges and Prospects

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1487
Author(s):  
Hadeel Alyenbaawi ◽  
W. Ted Allison ◽  
Sue-Ann Mok
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Chronic Traumatic Encephalopathy ◽  
Tissue Level ◽  
Therapeutic Approaches ◽  
Tau Pathology ◽  
The Brain

The accumulation of tau protein in the form of filamentous aggregates is a hallmark of many neurodegenerative diseases such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). These dementias share traumatic brain injury (TBI) as a prominent risk factor. Tau aggregates can transfer between cells and tissues in a “prion-like” manner, where they initiate the templated misfolding of normal tau molecules. This enables the spread of tau pathology to distinct parts of the brain. The evidence that tauopathies spread via prion-like mechanisms is considerable, but work detailing the mechanisms of spread has mostly used in vitro platforms that cannot fully reveal the tissue-level vectors or etiology of progression. We review these issues and then briefly use TBI and CTE as a case study to illustrate aspects of tauopathy that warrant further attention in vivo. These include seizures and sleep/wake disturbances, emphasizing the urgent need for improved animal models. Dissecting these mechanisms of tauopathy progression continues to provide fresh inspiration for the design of diagnostic and therapeutic approaches.

Lessons Learned From Coaching Postsecondary Students With Traumatic Brain Injury

2020 ◽  
Vol 5 (1) ◽  
pp. 88-96
Author(s):  
Mary R. T. Kennedy
Keyword(s):  
College Students ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sense Of Self ◽  
Scientific Evidence ◽  
Sudden Onset ◽  
Lessons Learned ◽  
Speech Language Pathologists ◽  
The Brain ◽  
Exhaustive List

Purpose The purpose of this clinical focus article is to provide speech-language pathologists with a brief update of the evidence that provides possible explanations for our experiences while coaching college students with traumatic brain injury (TBI). Method The narrative text provides readers with lessons we learned as speech-language pathologists functioning as cognitive coaches to college students with TBI. This is not meant to be an exhaustive list, but rather to consider the recent scientific evidence that will help our understanding of how best to coach these college students. Conclusion Four lessons are described. Lesson 1 focuses on the value of self-reported responses to surveys, questionnaires, and interviews. Lesson 2 addresses the use of immediate/proximal goals as leverage for students to update their sense of self and how their abilities and disabilities may alter their more distal goals. Lesson 3 reminds us that teamwork is necessary to address the complex issues facing these students, which include their developmental stage, the sudden onset of trauma to the brain, and having to navigate going to college with a TBI. Lesson 4 focuses on the need for college students with TBI to learn how to self-advocate with instructors, family, and peers.

Providing Care of Mild Traumatic Brain Injury by the Family Practice/Primary Care Optometrist

2018 ◽  
pp. 110-119
Keyword(s):  
Primary Care ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Family Practice ◽  
Advanced Training ◽  
Entry Level ◽  
The Family ◽  
Basic Understanding ◽  
The Brain

Primary Objectives: By extending the scope of knowledge of the primary care optometrist, the brain injury population will have expanded access to entry level neurooptometric care by optometric providers who have a basic understanding of their neurovisual problems, be able to provide some treatment and know when to refer to their colleagues who have advanced training in neuro-optometric rehabilitation.

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