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A review of laboratory and clinical data supporting the safety and efficacy of cyclosporin A in traumatic brain injury.

Abstract
For decades, cyclosporin A (CsA) has proved to be safe and effective for use in transplantation. In the past 10 years, this agent has shown neuroprotective effects in animal models of traumatic brain injury (TBI). This review article provides a critical overview of the literature on CsA neuroprotective effects in animal studies and current findings of clinical trials in the treatment of TBI with an emphasis on the possible CsA molecular mechanism of action. Animal data provide compelling evidence of the therapeutic benefits of CsA in TBI, but the outcome indices are heterogeneous with respect to the animal model of TBI as well as the route, dose, and timing of CsA administration. Similarly, clinical studies (phase II trials) adapting almost identical patient inclusion criteria have demonstrated the safety of CsA use in TBI, but the clinical trials are also heterogeneous based on study design, especially with regard to the variable timing of CsA administration after TBI. In view of the translational shortcomings of the preclinical studies and the rather pilot nature of the limited clinical trials that recently reached phase III, we offer guidance on the future directions of laboratory investigations on CsA that could improve the safety and efficacy of this agent in subsequent larger clinical trials.
AuthorsDzenan Lulic, Jack Burns, Eunkyung Cate Bae, Harry van Loveren, Cesar V Borlongan
JournalNeurosurgery (Neurosurgery) Vol. 68 Issue 5 Pg. 1172-85; discussion 1185-6 (May 2011) ISSN: 1524-4040 [Electronic] United States
PMID21307793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Neuroprotective Agents
  • Cyclosporine
Topics
  • Animals
  • Brain Injuries (drug therapy, epidemiology)
  • Clinical Trials as Topic (methods, trends)
  • Cyclosporine (adverse effects, therapeutic use)
  • Disease Models, Animal
  • Humans
  • Neuroprotective Agents (adverse effects, therapeutic use)
  • Treatment Outcome

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