The pathophysiology of traumatic brain injury at a glance

Prins, Mayumi L.; Greco, Tiffany; Alexander, Daya; Giza, Christopher C.

doi:10.1242/dmm.011585

Cited by 326 publications

(306 citation statements)

References 107 publications

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“…In the United States, it is estimated that 50,000 individuals die each year from TBI and 2.5-6.5 million individuals are living with the consequences of TBI, including debilitating physical, cognitive, and behavioral problems 1,2 . The consequences of TBI are not only due to primary mechanical injuries to the brain but also to secondary cellular and molecular injuries to the brain as well as other tissues that occur over time [3][4][5] . The development of approaches to diagnose and treat TBI has proven to be difficult because TBI is a complex disease process.…”

Section: Introductionmentioning

confidence: 99%

A Method to Inflict Closed Head Traumatic Brain Injury in <em>Drosophila</em>

Katzenberger

Loewen

Bockstruck

et al. 2015

JoVE

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Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies using Drosophila have contributed important breakthroughs in understanding neurological processes. Thus, with the goal of understanding the cellular and molecular basis of TBI pathologies in humans, we developed the High Impact Trauma (HIT) device to inflict closed head TBI in flies. Flies subjected to the HIT device display phenotypes consistent with human TBI such as temporary incapacitation and progressive neurodegeneration. The HIT device uses a spring-based mechanism to propel flies against the wall of a vial, causing mechanical damage to the fly brain. The device is inexpensive and easy to construct, its operation is simple and rapid, and it produces reproducible results. Consequently, the HIT device can be combined with existing experimental tools and techniques for flies to address fundamental questions about TBI that can lead to the development of diagnostics and treatments for TBI. In particular, the HIT device can be used to perform large-scale genetic screens to understand the genetic basis of TBI pathologies. Video LinkThe video component of this article can be found at

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Section: Introductionmentioning

confidence: 99%

A Method to Inflict Closed Head Traumatic Brain Injury in <em>Drosophila</em>

Katzenberger

Loewen

Bockstruck

et al. 2015

JoVE

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“…Positive effects of inhibition of LT synthesis in these studies can be explained by a different mechanism, severity, and extent of experimental TBI and non-traumatic brain injury caused by methanol poisoning. In TBI, focal or diffuse mechanical damage to the cerebral tissue causes an uncontrolled, excessive release of excitatory neurotransmitters, rapidly triggering a cascade of events called excitotoxicity [55]. Vascular damage in TBI leads to the infiltration of peripheral blood immune cells into brain tissue, which produce lipid inflammatory mediators, chemokines, inflammatory cytokines, and oxidative molecules.…”

Section: Discussionmentioning

confidence: 99%

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

Zakharov

Kotikova

Nurieva

et al. 2017

Clinical Toxicology

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Context: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. Objective: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. Methods: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. Results: The acute maximum (C max ) LT concentrations were higher than concentrations in survivors: C max for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4-0.5 pg/mL/h and peaked 4-5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. Conclusions: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.ARTICLE HISTORY

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“…23 A suggested mechanism of TBI-induced cell damage is of excess free radical generation produced by mitochondria. During normal metabolism, the tricarboxylic acid cycle (TCA) generates reducing equivalents to produce adenosine triphosphate (ATP).…”

Section: Discussionmentioning

confidence: 99%

Should an increase in cerebral neurochemicals following head kicks in full contact karate influence return to play?

Graham¹,

Pates²,

Davies

et al. 2015

Int J Immunopathol Pharmacol

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Background: Cerebral neurochemicals are markers of traumatic brain injury (TBI).Objectives: The aim of the study was to determine whether kicks to the head (KTH) in full contact karate significantly increased serum concentrations of protein S-100B, and neurone specific enolase (NSE). Kicks to the body (KTB) were also quantified to asses muscle tissue injury. Muscle damage was assessed by analysis of serum total creatine kinase (CK). Methods: Twenty-four full contact karate practitioners were observed and filmed during actual competition and divided into two main groups post event: (1) Kicks to the head and body group (KTH): n = 12; mean ± SD; age, 30.4 ± 6.7 years; height, 1.74 ± 0.1 m; weight, 79.1 ± 2.1 kg; and (2): Kicks to the body group (KTB): n = 12; mean ± SD; age, 28.2 ± 6.5 years; height, 1.75 ± 0.1 m; weight, 79.2 ± 1.7 kg. The KTH group received direct kicks to the head, while group KTB received kicks and punches to the body. Blood samples were taken before and immediately post-combat for analysis of serum S-100B, NSE, CK and cardiac troponin. Results: Significant increases in serum concentrations of S-100B (0.12 ± 0.17 vs. 0.37 ± 0.26, µg.L -1 ) and NSE (11.8 ± 4.1 vs. 20.2 ± 9.1 ng.mL -1 ) were encountered after combat in the KTH group and CK (123 ± 53 vs. 184 ± 103 U.L -1 ) in the KTB group (all P <0.05). Conclusions: Head kicks in full contact karate cause elevation of neurochemical markers associated with damaged brain tissue. The severity of injury is related to the early post-traumatic release of protein S-100B and NSE. The early kinetics and appearance post injury can reflect intracranial pathology, and suggest S-100B and NSE are extremely sensitive prognostic markers of TBI.

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The pathophysiology of traumatic brain injury at a glance

Cited by 326 publications

References 107 publications

A Method to Inflict Closed Head Traumatic Brain Injury in <em>Drosophila</em>

A Method to Inflict Closed Head Traumatic Brain Injury in <em>Drosophila</em>

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

Should an increase in cerebral neurochemicals following head kicks in full contact karate influence return to play?

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