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J Neurotrauma. 2018 Dec 1;35(23):2737-2754. doi: 10.1089/neu.2018.5778. Epub 2018 Aug 30.

Pre-Clinical Testing of Therapies for Traumatic Brain Injury.

Author information

1
1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas.
2
2 Department of Neurological Surgery, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
3
3 Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
4
4 Department of Anesthesiology and Critical Care, University of Pennsylvania , Philadelphia, Pennsylvania.
5
5 Department of Biomedical Engineering, Duke University , Durham, North Carolina.
6
6 Department of Neurological Surgery, The Miami Project to Cure Paralysis , Miami, Florida.
7
7 Department of Neurosurgery, Medical University of Pécs , Pécs, Hungary .
8
8 The Miami Project to Cure Paralysis, Leonard M. Miller School of Medicine, University of Miami , Miami, Florida.
9
9 Weill Institute for Neurosciences, Brain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California , San Francisco (UCSF), San Francisco, California.
10
10 Spinal Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky Medical Center , Lexington, Kentucky.
11
11 University of Florida, Virginia Commonwealth University, Banyan Biomarkers, Inc. , Alachua, Florida.
12
12 United States Army Medical Research and Materiel Command , Fort Detrick, Maryland.
13
13 Georgia Institute of Technology/Emory University , Atlanta, Georgia .
14
14 Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research , Silver Spring, Maryland.
15
15 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
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16 Department of Neurosciences, University of Messina , Via Consolare Valeria, Messina, Italy .
17
17 Departments of Neurology and Psychology, Dell Medical School, The University of Texas at Austin , Austin, Texas.
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18 Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy , Pittsburgh, Pennsylvania.
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19 Department of Neurosurgery, Baylor College of Medicine , Houston, Texas.
20
20 Spinal Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky , Lexington, Kentucky.
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21 Department of Medicine, Melbourne Brain Center, The University of Melbourne , Parkville, Victoria, Australia .
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22 Brain Trauma Neuroprotection Program, Walter Reed Army Institute of Research , Silver Spring, Maryland.
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23 Department of Neurosurgery, University of Pennsylvania , Philadelphia, Pennsylvania.
24
24 Department of Neurosurgery, Virginia Commonwealth University School of Medicine , Richmond, Virginia.
25
25 Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
26
26 Department of Biomedical Engineering, Wayne State University , Detroit, Michigan.

Abstract

Despite the large number of promising neuroprotective agents identified in experimental traumatic brain injury (TBI) studies, none has yet shown meaningful improvements in long-term outcome in clinical trials. To develop recommendations and guidelines for pre-clinical testing of pharmacological or biological therapies for TBI, the Moody Project for Translational Traumatic Brain Injury Research hosted a symposium attended by investigators with extensive experience in pre-clinical TBI testing. The symposium participants discussed issues related to pre-clinical TBI testing including experimental models, therapy and outcome selection, study design, data analysis, and dissemination. Consensus recommendations included the creation of a manual of standard operating procedures with sufficiently detailed descriptions of modeling and outcome measurement procedures to permit replication. The importance of the selection of clinically relevant outcome variables, especially related to behavior testing, was noted. Considering the heterogeneous nature of human TBI, evidence of therapeutic efficacy in multiple, diverse (e.g., diffuse vs. focused) rodent models and a species with a gyrencephalic brain prior to clinical testing was encouraged. Basing drug doses, times, and routes of administration on pharmacokinetic and pharmacodynamic data in the test species was recommended. Symposium participants agreed that the publication of negative results would reduce costly and unnecessary duplication of unsuccessful experiments. Although some of the recommendations are more relevant to multi-center, multi-investigator collaborations, most are applicable to pre-clinical therapy testing in general. The goal of these consensus guidelines is to increase the likelihood that therapies that improve outcomes in pre-clinical studies will also improve outcomes in TBI patients.

KEYWORDS:

guidelines; pre-clinical; traumatic brain injury

PMID:
29756522
DOI:
10.1089/neu.2018.5778

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