scholarly journals Differential Gene Expression Associated with Meningeal Injury in Acute Mild Traumatic Brain Injury

2017 ◽  
Vol 34 (4) ◽  
pp. 853-860 ◽  
Author(s):  
Whitney S. Livingston ◽  
Jessica M. Gill ◽  
Martin R. Cota ◽  
Anlys Olivera ◽  
Jessica L. O'Keefe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Differential Gene Expression ◽  
Mild Traumatic Brain Injury ◽  
Differential Gene

scholarly journals TT-301 Inhibits Microglial Activation and Improves Outcome after Central Nervous System Injury in Adult Mice

2012 ◽  
Vol 116 (6) ◽  
pp. 1299-1311 ◽  
Author(s):  
Michael L. James ◽  
Haichen Wang ◽  
Viviana Cantillana ◽  
Beilei Lei ◽  
Dawn N. Kernagis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Differential Gene Expression ◽  
Morris Water Maze ◽  
Water Maze ◽  
Murine Models ◽  
Differential Gene

Background Microglial inhibition may reduce secondary tissue injury and improve functional outcome following acute brain injury. Utilizing clinically relevant murine models of traumatic brain injury and intracerebral hemorrhage, neuroinflammatory responses and functional outcome were examined in the presence of a potential microglial inhibitor, TT-301. Methods TT-301 or saline was administered following traumatic brain injury or intracerebral hemorrhage, and then for four subsequent days. The effect of TT-301 on neuroinflammatory responses and neuronal viability was assessed, as well as short-term vestibulomotor deficit (Rotorod) and long-term neurocognitive impairment (Morris water maze). Finally differential gene expression profiles of mice treated with TT-301 were compared with those of vehicle. Results Reduction in F4/80+ staining was demonstrated at 1 and 10 days, but not 28 days, after injury in mice treated with TT-301 (n = 6). These histologic findings were associated with improved neurologic function as assessed by Rotorod, which improved by 52.7% in the treated group by day 7, and Morris water maze latencies, which improved by 232.5% as a function of treatment (n = 12; P < 0.05). Similar benefit was demonstrated following intracerebral hemorrhage, in which treatment with TT-301 was associated with functional neurologic improvement of 39.6% improvement in Rotorod and a reduction in cerebral edema that was independent of hematoma volume (n = 12; P < 0.05). Differential gene expression was evaluated following treatment with TT-301, and hierarchical cluster analysis implicated involvement of the Janus kinase-Signal Transducer and Activator of Transcription pathway after administration of TT-301 (n = 3/group). Conclusions Modulation of neuroinflammatory responses through TT-301 administration improved histologic and functional parameters in murine models of acute neurologic injury.

scholarly journals Early onset senescence and cognitive impairment in a murine model of repeated mTBI

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Nicole Schwab ◽  
YoungJun Ju ◽  
Lili-Naz Hazrati
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Dna Damage ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Cellular Senescence ◽  
Early Gene ◽  
Dna Breaks ◽  
Post Injury

AbstractMild traumatic brain injury (mTBI) results in broad neurological symptoms and an increased risk of being diagnosed with a neurodegenerative disease later in life. While the immediate oxidative stress response and post-mortem pathology of the injured brain has been well studied, it remains unclear how early pathogenic changes may drive persistent symptoms and confer susceptibility to neurodegeneration. In this study we have used a mouse model of repeated mTBI (rmTBI) to identify early gene expression changes at 24 h or 7 days post-injury (7 dpi). At 24 h post-injury, gene expression of rmTBI mice shows activation of the DNA damage response (DDR) towards double strand DNA breaks, altered calcium and cell–cell signalling, and inhibition of cell death pathways. By 7 dpi, rmTBI mice had a gene expression signature consistent with induction of cellular senescence, activation of neurodegenerative processes, and inhibition of the DDR. At both timepoints gliosis, microgliosis, and axonal damage were evident in the absence of any gross lesion, and by 7 dpi rmTBI also mice had elevated levels of IL1β, p21, 53BP1, DNA2, and p53, supportive of DNA damage-induced cellular senescence. These gene expression changes reflect establishment of processes usually linked to brain aging and suggests that cellular senescence occurs early and most likely prior to the accumulation of toxic proteins. These molecular changes were accompanied by spatial learning and memory deficits in the Morris water maze. To conclude, we have identified DNA damage-induced cellular senescence as a repercussion of repeated mild traumatic brain injury which correlates with cognitive impairment. Pathways involved in senescence may represent viable treatment targets of post-concussive syndrome. Senescence has been proposed to promote neurodegeneration and appears as an effective target to prevent long-term complications of mTBI, such as chronic traumatic encephalopathy and other related neurodegenerative pathologies.

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.

The Speech-Language Pathologists' Role in Mild Traumatic Brain Injury for Middle and High School–Age Children: Viewpoints on Guidelines From the Centers for Disease Control and Prevention

2019 ◽  
Vol 28 (3) ◽  
pp. 1363-1370 ◽  
Author(s):  
Jessica Brown ◽  
Katy O'Brien ◽  
Kelly Knollman-Porter ◽  
Tracey Wallace
Keyword(s):  
High School ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Disease Control ◽  
Mild Traumatic Brain Injury ◽  
School Age Children ◽  
School Age ◽  
Speech Language Pathologists ◽  
Control And Prevention ◽  
Centers For Disease Control

Purpose The Centers for Disease Control and Prevention (CDC) recently released guidelines for rehabilitation professionals regarding the care of children with mild traumatic brain injury (mTBI). Given that mTBI impacts millions of children each year and can be particularly detrimental to children in middle and high school age groups, access to universal recommendations for management of postinjury symptoms is ideal. Method This viewpoint article examines the CDC guidelines and applies these recommendations directly to speech-language pathology practices. In particular, education, assessment, treatment, team management, and ongoing monitoring are discussed. In addition, suggested timelines regarding implementation of services by speech-language pathologists (SLPs) are provided. Specific focus is placed on adolescents (i.e., middle and high school–age children). Results SLPs are critical members of the rehabilitation team working with children with mTBI and should be involved in education, symptom monitoring, and assessment early in the recovery process. SLPs can also provide unique insight into the cognitive and linguistic challenges of these students and can serve to bridge the gap among rehabilitation and school-based professionals, the adolescent with brain injury, and their parents. Conclusion The guidelines provided by the CDC, along with evidence from the field of speech pathology, can guide SLPs to advocate for involvement in the care of adolescents with mTBI. More research is needed to enhance the evidence base for direct assessment and treatment with this population; however, SLPs can use their extensive knowledge and experience working with individuals with traumatic brain injury as a starting point for post-mTBI care.

Assessment of Cognitive-Communicative Disorders of Mild Traumatic Brain Injury Sustained in Combat

2009 ◽  
Vol 19 (2) ◽  
pp. 47-57 ◽  
Author(s):  
Christine Parrish ◽  
Carole Roth ◽  
Brooke Roberts ◽  
Gail Davie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Psychological Health ◽  
Communication Disorders ◽  
Service Members ◽  
Patient Questionnaire ◽  
Speech Language Pathologists ◽  
Test Protocol ◽  
Communication Deficits

Abstract Background: Mild traumatic brain injury (mTBI) is recognized as the signature injury of the current conflicts in Iraq and Afghanistan, yet there remains limited understanding of the persisting cognitive deficits of mTBI sustained in combat. Speech-language pathologists (SLPs) have traditionally been responsible for evaluating and treating the cognitive-communication disorders following severe brain injuries. The evaluation instruments historically used are insensitive to the subtle deficits found in individuals with mTBI. Objectives: Based on the limited literature and clinical evidence describing traditional and current tests for measuring cognitive-communication deficits (CCD) of TBI, the strengths and weaknesses of the instruments are discussed relative to their use with mTBI. It is necessary to understand the nature and severity of CCD associated with mTBI for treatment planning and goal setting. Yet, the complexity of mTBI sustained in combat, which often co-occurs with PTSD and other psychological health and physiological issues, creates a clinical challenge for speech-language pathologists worldwide. The purpose of the paper is to explore methods for substantiating the nature and severity of CCD described by service members returning from combat. Methods: To better understand the nature of the functional cognitive-communication deficits described by service members returning from combat, a patient questionnaire and a test protocol were designed and administered to over 200 patients. Preliminary impressions are described addressing the nature of the deficits and the challenges faced in differentiating the etiologies of the CCD. Conclusions: Speech-language pathologists are challenged with evaluating, diagnosing, and treating the cognitive-communication deficits of mTBI resulting from combat-related injuries. Assessments that are sensitive to the functional deficits of mTBI are recommended. An interdisciplinary rehabilitation model is essential for differentially diagnosing the consequences of mTBI, PTSD, and other psychological and physical health concerns.

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