We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Viewpoint |

Neuroprotection After Traumatic Brain Injury

Ralf Watzlawick, MD1; David W. Howells, PhD2; Jan M. Schwab, MD, PhD3,4
[+] Author Affiliations
1Department of Neurology and Experimental Neurology, Spinal Cord Injury Research, Charité–Universitätsmedizin Berlin, Berlin, Germany
2Faculty of Heath, School of Medicine, University of Tasmania, Medical Sciences Precinct, Hobart, Tasmania, Australia
3Spinal Cord Injury Division, Department of Neurology, The Ohio State University, Wexner Medical Center, Columbus
4Department of Neuroscience and Center for Brain and Spinal Cord Repair, The Ohio State University, Wexner Medical Center, Columbus
JAMA Neurol. 2016;73(2):149-150. doi:10.1001/jamaneurol.2015.3627.
Text Size: A A A
Published online


This Viewpoint discusses the role of animal studies in clinical trials of neuroprotection in traumatic brain injury.

Is research on traumatic brain injury (TBI) repeating the failures seen in studies on neuroprotection in stroke? Recent failures of pivotal randomized clinical trials on neuroprotection in TBI resemble the costly setbacks experienced by stroke investigators that resulted in the cessation of interventional pharmacological trials and withdrawal of investment by the pharmaceutical industry. Many hypotheses have been advanced to explain these translational failures, such as methodological failures leading to false-positive results in animal studies or false-negative results in clinical trials or that animal models might not sufficiently recapitulate human TBI. To combat translational nihilism about the failures of these trials, we intend to provide a constructive analysis of what could be learned to improve translational prediction of future trials on neuroprotection in TBI.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview


Place holder to copy figure label and caption
Empirical Evidence of Reporting Bias of Progesterone Interventions in Experimental Traumatic Brain Injury Studies

A, The Egger regression line unmasks underlying bias by not intersecting the origin (respectively analyzed published data set4). B, Contour-enhanced funnel plot7 illustrates reporting bias (eg, publication bias). In case of absent bias, the experiments (dots) would be symmetrically distributed. Experiments missing in the core of the plot might be due to publication bias while dots missing in the dark gray area might be due to other reasons such as study quality. It appears that there are missing neutral or negative unpublished data that give a more realistic appraisal of the effects of progesterone. Contour lines indicating conventional levels of statistical significance (eg, <.01; .01<P<.05; .05<P<.1; P>.1) are added to the funnel plot demarcating distinct significance areas.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
A Brief Word About Quality

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Reliability of the MAST, CAGE, and AUDIT Questionnaires