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Published on: June 10, 2020
Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature
1Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands. j.w.schouten@erasmusmc.nl
Purpose Of Review:
Translating the efficacy of neuroprotective agents in experimental traumatic brain injury to clinical benefit has proven an extremely complex and, to date, unsuccessful undertaking. The focus of this review is on neuroprotective agents that have recently been evaluated in clinical trials and are currently under clinical evaluation, as well as on those that appear promising and are likely to undergo clinical evaluation in the near future.
Recent Findings:
Excitatory neurotransmitter blockage and magnesium have recently been evaluated in phase III clinical trials, but showed no neuroprotective efficacy. Cyclosporin A, erythropoietin, progesterone and bradykinin antagonists are currently under clinical investigation, and appear promising.
Summary:
Traumatic brain injury is a complex disease, and development of clinically effective neuroprotective agents is a difficult task. Experimental traumatic brain injury has provided numerous promising compounds, but to date these have not been translated into successful clinical trials. Continued research efforts are required to identify and test new neuroprotective agents, to develop a better understanding of the sequential activity of pathophysiologic mechanisms, and to improve the design and analysis of clinical trials, thereby optimizing chances for showing benefit in future clinical trials.
Insights
Developing neuroprotective agents for traumatic brain injury (TBI) has been challenging. While some agents show promise in clinical trials, translating experimental efficacy to patient benefit remains difficult.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- Translating experimental neuroprotective agents for traumatic brain injury (TBI) to clinical success is complex.
- Numerous promising compounds identified in experimental TBI models have not yet yielded successful clinical outcomes.
Purpose of the Study:
- To review neuroprotective agents recently evaluated in clinical trials for TBI.
- To discuss agents currently under clinical investigation for TBI.
- To highlight promising agents likely for future clinical evaluation in TBI.
Main Methods:
- Review of recent clinical trial data for neuroprotective agents in TBI.
- Analysis of ongoing clinical investigations for TBI therapeutics.
- Identification of potential future TBI drug candidates based on preclinical and early clinical data.
Main Results:
- Phase III trials of excitatory neurotransmitter blockers and magnesium showed no neuroprotective efficacy in TBI.
- Cyclosporin A, erythropoietin, progesterone, and bradykinin antagonists are currently under investigation and show promise for TBI.
- Despite experimental successes, clinical translation of neuroprotective agents for TBI remains limited.
Conclusions:
- Traumatic brain injury (TBI) is a complex condition, making the development of effective neuroprotective agents difficult.
- Continued research is essential to identify novel neuroprotective agents and understand TBI pathophysiology.
- Improving clinical trial design and analysis is crucial for optimizing the chances of demonstrating benefit in future TBI trials.
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