Experimental neurology
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Experimental neurology · Aug 2019
ReviewToward development of clinically translatable diagnostic and prognostic metrics of traumatic brain injury using animal models: A review and a look forward.
Traumatic brain injury is a leading cause of cognitive and behavioral deficits in children in the US each year. There is an increasing interest in both clinical and pre-clinical studies to discover biomarkers to accurately diagnose traumatic brain injury (TBI), predict its outcomes, and monitor its progression especially in the developing brain. In humans, the heterogeneity of TBI in terms of clinical presentation, injury causation, and mechanism has contributed to the many challenges associated with finding unifying diagnosis, treatment, and management practices. ⋯ This effort is possible through large scale collaborative research and data sharing across multiple centers. In addition, TBI causes dynamic deficits in multiple domains, and thus, a panel of biomarkers combining these measures to consider different deficits is more promising than a single biomarker for TBI. In this review, each of these tools are presented along with the clinical and pre-clinical findings, advantages, challenges and prospects of translating the pre-clinical knowledge into the human clinical setting.
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Experimental neurology · Jul 2019
ReviewDoes pediatric traumatic brain injury cause adult alcohol misuse: Combining preclinical and epidemiological approaches.
Traumatic brain injury (TBI) is closely interrelated with alcohol use disorders. This is mediated, in part, by the large number of individuals who are intoxicated at the time of their injuries. However, there is also evidence, both preclinically and epidemiologically that TBI, particularly when it occurs early in life can increase the incidence of alcohol use disorders later on. ⋯ In this review we discuss the epidemiological evidence for increased drinking in humans. Further, we discuss, the animal models for increased drinking after TBI and the potential mechanistic insights that have been derived from those animal models. We conclude, based on the framework described, that it is possible that pediatric TBI causes alcohol use disorders in humans.
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Experimental neurology · Jul 2019
ReviewTranslational approach towards determining the role of cerebral autoregulation in outcome after traumatic brain injury.
Cerebral autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, cerebral autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP) and thereby limit impairment of cerebral autoregulation and neurological deficits. ⋯ This review will describe translational studies using a more human like animal model (the pig) of TBI to identify better therapeutic strategies to improve outcome post injury. These studies also investigated the role of age and sex in outcome and mechanism(s) involved in improvement of outcome in the setting of TBI. Additionally, this review considers use of inhaled nitric oxide as a novel neuroprotective strategy in treatment of TBI.
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Experimental neurology · Dec 2018
ReviewCriteria to define mild, moderate, and severe traumatic brain injury in the mouse controlled cortical impact model.
Traumatic brain injury (TBI) is a major health concern in the United States resulting in a substantial number of hospitalizations and in a broad spectrum of symptoms and disabilities. In the clinical setting, neurological responsiveness and structural imaging are used to classify mild, moderate and severe TBI. To evaluate the complex secondary and severity-specific injury response, investigators have relied on pre-clinical rodent models. ⋯ Inconsistent with clinical evaluation, injury severity in the CCI model has predominately relied on the extent of tissue damage. In the present review, we discuss variations in surgical parameters for injury induction as well as the criteria used to determine injury severity. Additionally, we propose guiding principles for the induction and defining of mild, moderate and severe TBI in the craniectomy-dependent experimental mouse CCI model.
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Experimental neurology · Jan 2018
ReviewRapid identification and validation of novel targeted approaches for Glioblastoma: A combined ex vivo-in vivo pharmaco-omic model.
Tumor heterogeneity is a major factor in glioblastoma's poor response to therapy and seemingly inevitable recurrence. Only two glioblastoma drugs have received Food and Drug Administration approval since 1998, highlighting the urgent need for new therapies. Profiling "omics" analyses have helped characterize glioblastoma molecularly and have thus identified multiple molecular targets for precision medicine. ⋯ In that regard, high-throughput screening that allows for expedited preclinical drug testing and the use of GBM models that represent tumor heterogeneity more accurately than traditional cancer cell lines is necessary to maximize the successful translation of agents into the clinic. High-throughput screening has been successfully used in the testing, discovery, and validation of potential therapeutics in various cancer models, but it has not been extensively utilized in glioblastoma models. In this report, we describe the basic aspects of high-throughput screening and propose a modified high-throughput screening model in which ex vivo and in vivo drug testing is complemented by post-screening pharmacological, pan-omic analysis to expedite anti-glioma drugs' preclinical testing and develop predictive biomarker datasets that can aid in personalizing glioblastoma therapy and inform clinical trial design.