Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults

Wang, Hongcai; Sun, Congjian; Chen, Hai; Chen, Maosong; Shen, Gang; Ma, Yu‐Lan; Wang, Boding

doi:10.3109/02699052.2014.943288

Cited by 17 publications

(4 citation statements)

References 112 publications

(188 reference statements)

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“…Primary injuries result from direct mechanical forces to the brain that occur at the time of a traumatic event, whereas secondary injuries result from cellular and molecular mechanisms subsequently triggered in the brain and other tissues by primary injuries. TBI outcomes differ among individuals not only because they receive different primary injuries but also because their responses produce different secondary injuries (Wang et al 2014; Krishnamurthy and Laskowitz 2016). Therefore, a better understanding of secondary injury mechanisms and the connection between secondary injuries and outcomes is essential to advance the diagnosis and treatment of TBI.…”

mentioning

confidence: 99%

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

Katzenberger

Ganetzky

Wassarman

2016

G3 Genes|Genomes|Genetics

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Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes.

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confidence: 99%

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

Katzenberger

Ganetzky

Wassarman

2016

G3 Genes|Genomes|Genetics

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“…Traumatic brain injury (TBI) is a brain damage that accounts for a large number of long-term disability cases and premature deaths and is associated with cognitive decline and neurodegeneration [1, 2]. Immediately after the initial impact, brains suffer from primary injuries such as damage to the neurovascular system and contusion, which are followed by secondary injuries that impair critical cellular processes [3]. Current treatments of TBI are main symptomatic treatments such as anticoagulants, anticonvulsants, and rehabilitation therapies and vary according to the severity of the symptoms.…”

Section: Introductionmentioning

confidence: 99%

Silencing of TRIM44 Inhibits Inflammation and Alleviates Traumatic Brain Injury in Rats by Downregulating TLR4-NF-κB Signaling

Zhu¹,

Dong²,

Yue³

et al. 2022

Neuroimmunomodulation

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Background: Neuroinflammation subsequent to traumatic brain injury (TBI) is important for the recovery of patients and is associated with neurodegenerative changes post-TBI. The tripartite motif containing 44 (TRIM44) protein is an E3 ligase involved in the regulation of immune function with no previously known link to TBI. This study explores the connection between TRIM44 and TBI. Methods: After induction of TBI in rats by control cortex injury, TRIM44 expressions were determined with quantitative real-time reverse transcription polymerase chain reaction and Western blot, and Toll-like receptor 4 (TLR4)-NF-κB signaling was examined by the expression of TLR4, p65 phosphorylation, and the specific NF-κB transcription activity. The effects of TRIM44 knockdown on inflammation, neurological function, and TLR4-NF-κB signaling in TBI rats were revealed by the detection of proinflammatory cytokines and TLR4-NF-κB signaling molecules, modified neurological severity score, brain water content, and Evans blue permeability. Results: We found that TRIM44 expression was significantly increased following TBI induction along with TLR4-NF-κB activation. Silencing of TRIM44 suppressed proinflammatory cytokine production, improved neurological outcomes, alleviated brain edema, and inhibited TLR4-NF-κB signaling in TBI rats. Conclusion: Our findings suggest that suppressing TRIM44 or modulation of relevant pathways may be a therapeutic strategy for TBI.

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“…Indeed, there are reasons to believe that changes in the brain's ability to maintain homeostasis may itself contribute to additional brain injury. (5) One condition affecting the homeostatic response to injury is paroxysmal sympathetic hyperactivity (PSH). (6) PSH is common, affecting an estimated 8-25% or severe TBI survivors.…”

Section: Introductionmentioning

confidence: 99%

Catecholamines and Paroxysmal Sympathetic Hyperactivity after Traumatic Brain Injury

Fernandez-OrtegaJuan¹,

BaguleyIan

GatesThomas

et al. 2017

Journal of Neurotrauma

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Paroxysmal sympathetic hyperactivity (PSH) affects a significant minority of people in the intensive care unit after severe traumatic brain injury. Systematic research has yet to elucidate or quantify the extent of the role of the catecholamines or adrenocortical and thyroid axis hormonal influences in the condition. Data were prospectively collected on 80 consecutive patients, 18 of whom developed clinical signs of PSH (22.5%). Catecholamine and hormonal data were collected sequentially at 4-h intervals or during and between episodes of PSH. Evaluated variables showed 200-300% increases in catecholamines and, to a lesser extent, adrenocortical hormones during paroxysms. The majority of PSH episodes (72%) were noted to be in response to an observable triggering event. These changes were not observed in subjects without PSH. These data go some way to explain why PSH produces adverse consequences in survivors of TBI with the condition.

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Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults

Cited by 17 publications

References 112 publications

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

Silencing of TRIM44 Inhibits Inflammation and Alleviates Traumatic Brain Injury in Rats by Downregulating TLR4-NF-κB Signaling

Catecholamines and Paroxysmal Sympathetic Hyperactivity after Traumatic Brain Injury

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