Modest cooling therapies (35ºC to 37.5ºC) for traumatic brain injury

Saxena, Manoj; Andrews, Peter; Cheng, Andrew; Deol, Kiran; Hammond, Naomi

doi:10.1002/14651858.cd006811.pub3

Cited by 17 publications

(10 citation statements)

References 24 publications

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“…Unfortunately, each trial failed to show benefit; several therapies were deleterious. 10–17 We therefore propose in this review a new framework to guide future preclinical and clinical trials to optimize the immune response to TBI:…”

Section: Introduction and Overviewmentioning

confidence: 99%

The far-reaching scope of neuroinflammation after traumatic brain injury

et al. 2017

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The “silent epidemic” of traumatic brain injury (TBI) has been placed in the spotlight following investigations and popular press coverage of athletes and returning soldiers with single and repetitive injuries; however, treatments to improve the outcome for patients with TBI across the spectrum from mild to severe TBI are lacking. Neuroinflammation may cause acute secondary injury after TBI, and it has been linked to chronic neurodegenerative diseases. Despite these findings, anti-inflammatory agents have failed to improve outcomes in clinical trials. We therefore propose in this review a new framework for future exploration of targeted immunomodulation after TBI that incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options. Structured around the dynamics of the immune response to TBI – from initial triggers to chronic neuroinflammation – the ability of soluble and cellular inflammatory mediators to promote repair and regeneration versus secondary injury and neurodegeneration is highlighted, with knowledge from human studies explicitly defined throughout this review. Recent advances in neuroimmunology and TBI-responsive neuroinflammation are incorporated, including inflammasomes, mechanisms of microglial polarization, and glymphatic clearance. In addition, we identify throughout this review where these findings may offer novel therapeutic targets for translational and clinical research, incorporate evidence from other brain injury models, and identify outstanding questions in the field.

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Section: Introduction and Overviewmentioning

confidence: 99%

The far-reaching scope of neuroinflammation after traumatic brain injury

et al. 2017

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“…Furthermore, they reported that males and females respond differently to post‐traumatic hypothermia after TBI; overall contusion volume was significantly reduced in males but not in females (Suzuki et al, ). This finding is especially important because the debate about the clinical benefits of therapeutic hypothermia continues, with recent randomized control trials in adults and children actually that suggesting hypothermia could cause more harm than benefit (Saxena et al, ; Andrews et al, ; Maekawa et al, ). However, these trials, like many others in TBI research, failed to separate and analyze sex differences, which the data from Suzuki et al () suggest could be a critical element in the role of therapeutic hypothermia in TBI.…”

Section: Therapeutic Hypothermiamentioning

confidence: 99%

Do microglia play a role in sex differences in TBI?

Caplan¹,

Cox²,

Bedi³

2016

J of Neuroscience Research

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Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality for both males and females and is, thus, a major focus of current study. Although the overall death rate of TBI for males is roughly three times higher than that for females, males have been disproportionately represented in clinical and preclinical studies. Gender differences are known to exist in many neurologic disorders, such as multiple sclerosis and stroke, and differences appear to exist in TBI. Furthermore, it is known that microglia have sexually dimorphic roles in CNS development and other neurologic conditions; however, most animal studies of microglia and TBI have focused on male subjects. Microglia are a current target of many preclinical and clinical therapeutic trials for TBI. Understanding the relationship among sex, sex hormones, and microglia is critical to truly understanding the pathophysiology of TBI. However, the evidence for sex differences in TBI centers mainly on sex hormones, and evidenced-based conclusions are often contradictory. In an attempt to review the current literature, it is apparent that sex differences likely exist, but the contradictory nature and magnitude of such differences in the existing literature does not allow definite conclusions to be drawn, except that more investigation of this issue is necessary. © 2016 Wiley Periodicals, Inc.

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“…A review by Cochrane and colleagues concluded that there is no evidence that induced hypothermia is beneficial in the treatment of traumatic head injury [ 339 ]. In addition, it suggested that there is an increase in pulmonary infections with the intervention of hypothermia compared to controls [ 340 ]. While considering the numerous variables in different clinical trials, the Brain Trauma Foundation states that six clinical tries of moderate quality did not clearly associate hypothermia with consistent and statistically significant reductions in mortality, but did find benefit in the fact that the same patients were more likely to have favorable neurological outcomes, defined as GCS scores of 4 or 5.…”

Section: Treatment Strategies and Modalities After Tbimentioning

confidence: 99%

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

Reis

Wang

Akyol

et al. 2015

IJMS

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Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI.

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Modest cooling therapies (35ºC to 37.5ºC) for traumatic brain injury

Cited by 17 publications

References 24 publications

The far-reaching scope of neuroinflammation after traumatic brain injury

The far-reaching scope of neuroinflammation after traumatic brain injury

Do microglia play a role in sex differences in TBI?

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

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