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Animal modeling of traumatic brain injury in pre-clinical drug development: where do we go from here?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
2011 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 164, no 4, 1207-1229 p.Article in journal (Refereed) Published
Abstract [en]

Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Survivors of TBI frequently suffer from long term personality changes and deficits in cognitive and motor performance, urgently calling for novel pharmacological treatment options. To date, all clinical trials evaluating neuroprotective compounds have failed in demonstrating clinical efficacy in cohorts of severely injured TBI patients. The purpose of the present review is to describe the utility of animal models of TBI for pre-clinical evaluation of pharmacological compounds. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. To successfully develop compounds for clinical TBI, a thorough evaluation in several TBI models and injury severities is crucial. Additionally, brain pharmacokinetics and the time window must be carefully evaluated. Although the search for a single-compound, "silver bullet" therapy is ongoing, a combination of drugs targeting various aspects of neuroprotection, neuroinflammation and regeneration may be needed. In summary, finding drugs and prove clinical efficacy in TBI is a major challenge ahead for the research community and the drug industry. For a successful translation of basic science knowledge to the clinic to occur we believe that a further refinement of animal models and functional outcome methods is important. In the clinical setting, improved patient classification, more homogenous patient cohorts in clinical trials, standardized treatment strategies, improved CNS drug delivery systems and monitoring of target drug levels and drug effects is warranted.

Place, publisher, year, edition, pages
2011. Vol. 164, no 4, 1207-1229 p.
Keyword [en]
Traumatic brain injury, review, neuroprotection, magnesium, yclosporin, glutamate, reactive oxygen species, inflammation, plasticity, animal modeling, contusion
National Category
Surgery
Research subject
Neurosurgery
Identifiers
URN: urn:nbn:se:uu:diva-146230DOI: 10.1111/j.1476-5381.2010.01163.xISI: 000295218600009PubMedID: 21175576OAI: oai:DiVA.org:uu-146230DiVA: diva2:397768
Available from: 2011-02-15 Created: 2011-02-15 Last updated: 2017-12-11Bibliographically approved

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