Journal of neurotrauma
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Journal of neurotrauma · Nov 2020
ReviewIntracranial Pressure Monitoring in Experimental Traumatic Brain Injury: Implications for Clinical Management.
Traumatic brain injury (TBI) is often associated with long-term disability and chronic neurological sequelae. One common contributor to unfavorable outcomes is secondary brain injury, which is potentially treatable and preventable through appropriate management of patients in the neurosurgical intensive care unit. Intracranial pressure (ICP) is currently the predominant neurological-specific physiological parameter used to direct the care of severe TBI (sTBI) patients. ⋯ The detailed cellular and molecular derangements associated with intracranial hypertension (IC-HTN) and their relationship to injury phenotype and neurological outcomes are not completely understood. Various animal models of TBI have been developed, but the clinical applicability of ICP monitoring in the pre-clinical setting has not been well-characterized. Linking basic mechanistic studies in translational TBI models with investigation of ICP monitoring that more faithfully replicates the clinical setting will provide clinical investigators with a more informed understanding of the pathophysiology of IC-HTN, thus facilitating development of improved therapies for sTBI patients.
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Journal of neurotrauma · Nov 2020
ReviewData Dissemination: Shortening the Long Tail of Traumatic Brain Injury Dark Data.
Translation of traumatic brain injury (TBI) research findings from bench to bedside involves aligning multi-species data across diverse data types including imaging and molecular biomarkers, histopathology, behavior, and functional outcomes. In this review we argue that TBI translation should be acknowledged for what it is: a problem of big data that can be addressed using modern data science approaches. We review the history of the term big data, tracing its origins in Internet technology as data that are "big" according to the "4Vs" of volume, velocity, variety, veracity and discuss how the term has transitioned into the mainstream of biomedical research. ⋯ Throughout our discussion we highlight the need to pull data from diverse sources including unpublished data ("dark data") and "long-tail data" (small, specialty TBI datasets undergirding the published literature). We review a few early examples of published articles in both the pre-clinical and clinical TBI research literature to demonstrate how data reuse can drive new discoveries leading into translational therapies. Making TBI data resources more Findable, Accessible, Interoperable, and Reusable (FAIR) through better data stewardship has great potential to accelerate discovery and translation for the silent epidemic of TBI.
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Journal of neurotrauma · Nov 2020
ReviewPaths to successful translation of new therapies for severe TBI in the golden age of traumatic brain injury research: A Pittsburgh vision.
New neuroprotective therapies for severe traumatic brain injury (TBI) have not translated from pre-clinical to clinical success. Numerous explanations have been suggested in both the pre-clinical and clinical arenas. Coverage of TBI in the lay press has reinvigorated interest, creating a golden age of TBI research with innovative strategies to circumvent roadblocks. ⋯ TBI research from concussion to coma can cross-pollinate and further advancement of new therapies. Misconceptions can stifle/misdirect TBI research and deserve special attention. Finally, we synthesize an approach to deliver therapeutic breakthroughs in this golden age of TBI research.
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Journal of neurotrauma · Nov 2020
ReviewThe Clinical Relevance of Behavior Testing in Animal Models of Traumatic Brain Injury.
Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, with patients often suffering from consequences such as cognitive deficits, social abnormalities, anxiety, depression, pain, and motor dysfunction. Given that these impairments often have a significant impact on the patient's quality of life, a key aim of therapeutic intervention in TBI is to mitigate these effects. Translational strategies to develop such interventions have heavily featured animal models of TBI. ⋯ However, in light of the past translational failures that have plagued the TBI field, the clinical relevance of these preclinical behavioral tests is now being scrutinized. This article will summarize the behavioral consequences of TBI in humans; describe common methods available for testing cognition, social function, motor ability, pain, as well as depression- and anxiety-like behaviors in animal models of TBI; provide an overview of the results from TBI animal model studies that have utilized these methods; and discuss these pre-clinical behavior methods and findings in terms of their relevance to the clinical TBI setting. We conclude that there is translational value in these methods and their related findings, but also suggest strategies and future research to improve the clinical relevance of behavior testing in animal models of TBI.
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Journal of neurotrauma · Nov 2020
ReviewImproving Understanding and Outcomes of Traumatic Brain Injury Using Bidirectional Translational Research.
Recent clinical trials in traumatic brain injury (TBI) have failed to demonstrate therapeutic effects even when there appears to be good evidence for efficacy in one or more appropriate pre-clinical models. While existing animal models mimic the injury, difficulties in translating promising therapeutics are exacerbated by the lack of alignment of discrete measures of the underlying injury pathology between the animal models and human subjects. To address this mismatch, we have incorporated reverse translation of bedside experience to inform pre-clinical studies in a large animal (pig) model of TBI that mirror practical clinical assessments. ⋯ The cerebral effects of these clinically commonly used vasoactive agents are not known. This review will emphasize pediatric work and will describe bidirectional translational studies using a more human-like animal model of TBI to identify better therapeutic strategies to improve outcome post-injury. These studies in addition investigated the mechanism(s) involved in improvement of outcome in the setting of TBI.