scholarly journals Single-Cell Profiling Resolved Transcriptional Alterations and Lineage Dynamics of Subventricular Zone after Mild Traumatic Brain Injury

2021 ◽  
Author(s):  
Xiameng Chen ◽  
Shuqiang Cao ◽  
Yinji Wang ◽  
Manrui Li ◽  
Yadong Guo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Single Cell ◽  
Mild Traumatic Brain Injury ◽  
Subventricular Zone ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Molecular Alterations ◽  
Cell Diversity ◽  
Transcriptional Alterations

Mild traumatic brain injury (mTBI) is the most common form of brain trauma caused by physical impact. The subventricular zone (SVZ) is a neurogenetic niche that contributes to homeostasis and repair after brain injury. It is particularly challenging to fully elucidate the molecular alterations in the SVZ occurring in response to injury due to its cell diversity and the complex network. In this study, we aimed to address this issue using a novel transcriptomic technique- unbiased single-cell RNA sequencing. We resolved previous unknown cell subpopulations harbored in the niche, and uncovered cell type-specific alterations in gene expression, enriched pathways, and cell-cell crosstalk following mTBI. Notably, we also report novel lineage trajectories and molecular hallmarks that govern neurogenesis. This study dissects the delicate transcriptome changes of individual cell types as well as the reprogramming process of cells in the SVZ niche after mTBI, and our findings are expected to facilitate the development of therapeutic interventions or diagnostic tests for mTBI.

scholarly journals Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury

2014 ◽  
Vol 121 (6) ◽  
pp. 1342-1350 ◽  
Author(s):  
Rebekah Mannix ◽  
Jacqueline Berglass ◽  
Justin Berkner ◽  
Philippe Moleus ◽  
Jianhua Qiu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Memory ◽  
Mild Traumatic Brain Injury ◽  
Exploratory Behavior ◽  
Clinical Syndrome ◽  
Therapeutic Interventions ◽  
Behavioral Testing ◽  
Behavioral Deficits ◽  
Structural Brain Damage

Object With the recent increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions), several models of rmTBI have been established. Characterizing these models in terms of behavioral and histopathological outcomes is vital to assess their clinical translatability. The purpose of this study is to provide an in-depth behavioral and histopathological phenotype of a clinically relevant model of rmTBI. Methods The authors used a previously published weight-drop model of rmTBI (7 injuries in 9 days) in 2- to 3-month-old mice that produces cognitive deficits without persistent loss of consciousness, seizures, gross structural imaging findings, or microscopic evidence of structural brain damage. Injured and sham-injured (anesthesia only) mice were subjected to a battery of behavioral testing, including tests of balance (rotarod), spatial memory (Morris water maze), anxiety (open field plus maze), and exploratory behavior (hole-board test). After behavioral testing, brains were assessed for histopathological outcomes, including brain volume and microglial and astrocyte immunolabeling. Results Compared with sham-injured mice, mice subjected to rmTBI showed increased exploratory behavior and had impaired balance and worse spatial memory that persisted up to 3 months after injury. Long-term behavioral deficits were associated with chronic increased astrocytosis and microgliosis but no volume changes. Conclusions The authors demonstrate that their rmTBI model results in a characteristic behavioral phenotype that correlates with the clinical syndrome of concussion and repetitive concussion. This model offers a platform from which to study therapeutic interventions for rmTBI.

scholarly journals Single Cell Molecular Alterations Reveal Pathogenesis and Targets of Concussive Brain Injury

2018 ◽  
Author(s):  
Douglas Arneson ◽  
Yumei Zhuang ◽  
Hyae Ran Byun ◽  
In Sook Ahn ◽  
Zhe Ying ◽  
...  
Keyword(s):  
Brain Injury ◽  
Single Cell ◽  
Cell Types ◽  
Single Cell Sequencing ◽  
Molecular Alterations ◽  
Hippocampal Dysfunction ◽  
Behavioral Abnormalities ◽  
Sequencing Method ◽  
A Cell ◽  
Cell Type Specific

ABSTRACTThe complex neuropathology of traumatic brain injury (TBI) is difficult to dissect in the hippocampus considering the convoluted hippocampal cytoarchitecture. As a major casualty of TBI, hippocampal dysfunction results in cognitive decline that may escalate to other neurological disorders, and the molecular basis is hidden in the genomic programs of individual hippocampal cells. Using the unbiased single cell sequencing method Drop-seq, we uncovered the hippocampal cell types most sensitive to concussive mild TBI (mTBI) as well as the vulnerable genes, pathways and cell-cell interactions predictive of disease pathogenesis in a cell-type specific manner, revealing hidden pathogenic mechanisms and potential targets. Targeting Ttr, encoding the thyroid hormone T4 transporter transthyretin, mitigated the genomic and behavioral abnormalities associated with mTBI. Single cell genomics provides unique evidence about altered circuits and pathogenic pathways, and pinpoints new targets amenable to therapeutics in mTBI and related disorders.

scholarly journals Integration of single-cell and bulk RNA sequencing data reveals key cell types and regulators in traumatic brain injury

2021 ◽  
Vol 18 (2) ◽  
pp. 1201-1214
Author(s):  
Rui-zhe Zheng ◽  
◽  
Jin Xing ◽  
Qiong Huang ◽  
Xi-tao Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Types ◽  
Sequencing Data

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.

Posttraumatic Stress Disorder Exacerbates Emotional Complaints but not Cognitive Impairments in Individuals Suffering from Postconcussional Disorder after Mild Traumatic Brain Injury

2015 ◽  
Vol 26 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Sara C. Schroeder ◽  
Ronald M. Ruff ◽  
Lutz Jäncke
Keyword(s):  
Traumatic Brain Injury ◽  
Posttraumatic Stress Disorder ◽  
Brain Injury ◽  
Posttraumatic Stress ◽  
Mild Traumatic Brain Injury ◽  
Test Performance ◽  
Stress Disorder ◽  
Negative Impact ◽  
Neuropsychological Test ◽  
Composite Scale

The aim of this study was to examine the effect of posttraumatic stress disorder (PTSD) on (a) neuropsychological test performance and (b) self-reported emotional complaints within individuals suffering from postconcussional disorder (PCD) after a mild traumatic brain injury (MTBI). A two-group comparative research design was employed. Two MTBI samples with and without PTSD were assessed with a neuropsychological test battery and the Ruff Neurobehavioral Inventory (RNBI). On the neurocognitive test performances no significant between group differences were found, but the MTBI group with PTSD endorsed a significantly greater number of emotional complaints, especially in the RNBI subscales of anxiety and depression. The patients with PTSD also endorsed a significantly greater number of premorbid sequelae in the RNBI emotional composite scale as well as the RNBI premorbid subscales of pain, anxiety and abuse. In sum, PTSD has a negative impact on emotional but not cognitive functioning within individuals suffering from PCD after a mild TBI.

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