The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome

McDonald, Stuart J.; Sun, Mujun; Agoston, Denes V.; Shultz, Sandy R.

doi:10.1186/s12974-016-0555-1

Cited by 106 publications

(86 citation statements)

References 92 publications

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“…Yet, case fatality rates in severe TBI have not decreased significantly since 1990 [30], remaining with an outstanding mortality, because up to 50% of the patients will still die and nearly all survivors will present some degree of sequelae [3,4,6,[31][32][33]. To the present, regardless of over dozens of phase III clinical trials, there are no specific treatments known to improve TBI outcomes [13]. Hence, TBI is heterogeneous in terms of pathophysiology, clinical presentation, and outcome, with case fatality rates ranging from <1% in mild TBI up to 50% in severe TBI.…”

Section: Tbi Is Classified By Different Methods; In the 1970s Teasdamentioning

confidence: 99%

“…Based on GCS, TBI is classified into mild (GCS score [14][15], moderate (9)(10)(11)(12)(13), and severe (3-8) [15]. At present, GCS is the most used method for TBI classification, however, has a number of limitations [15,16].…”

Section: Tbi Is Classified By Different Methods; In the 1970s Teasdamentioning

confidence: 99%

“…The ongoing brain damage characteristic of secondary injury culminates in notable cell death [24,40,41]. Typically, initial neuronal death following acute brain injury occurs by necrosis, on a time scale of minutes, then, a second wave of delayed cell death occurs mostly by apoptosis [13,[42][43][44][45]. Indeed, this protracted course of cell death following TBI may represent a unique opportunity for therapeutic intervention.…”

Section: Mechanisms Of Neural Injury In the Traumatic Penumbramentioning

confidence: 99%

“…Modulating these inflammatory cells by changing their phenotype from pro-inflammatory to anti-inflammatory would likely promote therapeutic effects on TBI [42,59,98]. Additionally, peripheral injuries of the multi-injured patient may increase circulating levels of many of the inflammatory cytokines worsening TBI outcomes [13,68].…”

Section: Mechanisms Of Neural Injury In the Traumatic Penumbramentioning

confidence: 99%

“…Blunt trauma accounts for about 88-95% of TBI cases, whereas the remaining 5-12% of cases are the result of penetrating injuries [12]. Because of the high-impact nature of trauma-inducing accidents, patients commonly suffer concomitant injuries to multiple body regions and organs, otherwise known as multitrauma or polytrauma, that are capable of modifying the pathobiology and outcomes of TBI [13].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Regner¹,

Meirelles²,

Simon³

2018

Traumatic Brain Injury - Pathobiology, Advanced Diagnostics and Acute Management

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Understanding the pathophysiology of TBI is crucial for the development of more effective therapeutic strategies. At the moment of the traumatic impact, transfer of kinetic forces causes neurologic damage; this primary injury triggers a secondary wave of biochemical cascades, together with metabolic and cellular changes, called secondary neural injury. These areas of ongoing secondary injury, or areas of "traumatic penumbra," represent crucial targets for therapeutic interventions. This chapter is focused on the interplay between progression of parenchymal injury and the neuroprotective and neurorestorative processes that are emerging and developing subsequently to traumatic impact. Thus, we emphasized the role of traumatic penumbra in TBI pathogenesis and suggested a crucial contribution of the neurovascular units (NVUs) and paracrine effects of exosomes and miRNAs in promoting neurological recovery.

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Section: Tbi Is Classified By Different Methods; In the 1970s Teasdamentioning

confidence: 99%

Section: Tbi Is Classified By Different Methods; In the 1970s Teasdamentioning

confidence: 99%

Section: Mechanisms Of Neural Injury In the Traumatic Penumbramentioning

confidence: 99%

Section: Mechanisms Of Neural Injury In the Traumatic Penumbramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Regner¹,

Meirelles²,

Simon³

2018

Traumatic Brain Injury - Pathobiology, Advanced Diagnostics and Acute Management

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Early vs Late Fixation of Extremity Fractures Among Adults With Traumatic Brain Injury

Zheng,

Ouyang,

Zhang

et al. 2024

JAMA Netw Open

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ImportanceThe optimal timing for fixation of extremity fractures after traumatic brain injury (TBI) remains controversial.ObjectiveTo investigate whether patients who underwent extremity fixation within 24 hours of TBI experienced worse outcomes than those who had the procedure 24 hours or more after TBI.Design, Setting, and ParticipantsThis cohort study used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Patients 16 years or older with TBI who underwent internal extremity fixation met inclusion criteria. To compare outcomes, patients who underwent the procedure within 24 hours were propensity score matched with those who underwent it 24 hours or later. Patients were treated from December 9, 2014, to December 17, 2017. Data analysis was conducted between August 1, 2022, and December 25, 2023.Main Outcomes and MeasuresThe primary outcome was an unfavorable functional status at 6 months (Glasgow Outcome Scale–Extended [GOSE] score ≤4).ResultsA total of 253 patients were included in this study. The median age was 41 (IQR, 27-57) years, and 184 patients (72.7%) were male. The median Injury Severity Score (ISS) was 41 (IQR, 27-49). Approximately half of the patients (122 [48.2%]) had a mild TBI while 120 (47.4%) had moderate to severe TBI. Seventy-four patients (29.2%) underwent an internal extremity fixation within 24 hours, while 179 (70.8%) had the procedure 24 hours or later. At 6 months, 86 patients (34.0%) had an unfavorable functional outcome. After propensity score matching, there were no statistically significant differences in unfavorable functional outcomes at 6 months (odds ratio [OR], 1.12 [95% CI, 0.51-1.99]; P = .77) in patients with TBI of any severity. Similar results were observed in patients with mild TBI (OR, 0.71 [95% CI, 0.22-2.29]; P = .56) and moderate to severe TBI (OR, 1.08 [95% CI, 0.32-3.70]; P = .90).Conclusions and RelevanceThe outcomes of extremity fracture fixation performed within 24 hours after TBI appear not to be worse than those of procedures performed 24 hours or later. This finding suggests that early fixation after TBI could be considered in patients with mild head injuries.

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A Rapid Neurological Assessment Protocol for Repeated Mild Traumatic Brain Injury in Awake Rats

et al. 2019

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Preclinical models for mild traumatic brain injury (mTBI) need to recapitulate several essential clinical features associated with mTBI, including a lack of significant neuropathology and the onset of neurocognitive symptoms normally associated with mTBI. Here we show how to establish a protocol for reliably and repeatedly inducing a mild awake closed head injury (ACHI) in rats, with no mortality or clinical indications of persistent pain. Moreover, we implement a new rapid neurological assessment protocol (NAP) that can be completely conducted within 1 min of each impact. This ACHI model will help to rectify the paucity of data on how repeated mTBI (r-mTBI) impacts the juvenile brain, an area of significant concern in clinical populations where there is evidence that behavioral sequelae following injury can be more persistent in juveniles. In addition, the ACHI model can help determine if r-mTBI early in life can predispose the brain to exhibiting greater neuropathology (i.e., chronic traumatic encephalopathy) later in life and can facilitate the identification of critical periods of vulnerability to r-mTBI across the lifespan. This article describes the protocol for administering an awake closed head mTBI (i.e., ACHI) to rats, as well as how to perform a rapid NAP following each ACHI. Methods for administering the ACHI to individual subjects repeatedly are described, as are the methods and scoring system for the NAP. The goal of this article is to provide a standardized set of procedures allowing the ACHI and NAP protocols to be used reliably by different laboratories. C 2019 by John Wiley & Sons, Inc.Keywords: behavior r concussion r head trauma r mild traumatic brain injury (2019). A rapid neurological assessment protocol for repeated mild traumatic brain injury in awake rats.

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The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome

Cited by 106 publications

References 92 publications

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Early vs Late Fixation of Extremity Fractures Among Adults With Traumatic Brain Injury

A Rapid Neurological Assessment Protocol for Repeated Mild Traumatic Brain Injury in Awake Rats

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