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Animal modelling of traumatic brain injury in preclinical drug development : where do we go from here?

Marklund, Niklas LU and Hillered, Lars (2011) In British Journal of Pharmacology 164(4). p.29-1207
Abstract

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 preclinical 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... (More)

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 preclinical 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 central nervous system drug delivery systems and monitoring of target drug levels and drug effects is warranted.

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author
organization
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Brain Injuries, Disease Models, Animal, Drug Evaluation, Preclinical, Female, Humans, Male, Mice, Neuroprotective Agents, Rats, Translational Medical Research, Treatment Outcome, Journal Article, Research Support, Non-U.S. Gov't, Review
in
British Journal of Pharmacology
volume
164
issue
4
pages
29 - 1207
publisher
The British Pharmacological Society
external identifiers
  • scopus:80053317403
ISSN
1476-5381
DOI
10.1111/j.1476-5381.2010.01163.x
language
English
LU publication?
no
id
8c7d54c0-c125-4456-b58a-d00eb8d27f59
date added to LUP
2018-03-03 15:08:52
date last changed
2018-11-18 05:03:23
@article{8c7d54c0-c125-4456-b58a-d00eb8d27f59,
  abstract     = {<p>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 preclinical 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 central nervous system drug delivery systems and monitoring of target drug levels and drug effects is warranted.</p>},
  author       = {Marklund, Niklas and Hillered, Lars},
  issn         = {1476-5381},
  keyword      = {Animals,Brain Injuries,Disease Models, Animal,Drug Evaluation, Preclinical,Female,Humans,Male,Mice,Neuroprotective Agents,Rats,Translational Medical Research,Treatment Outcome,Journal Article,Research Support, Non-U.S. Gov't,Review},
  language     = {eng},
  number       = {4},
  pages        = {29--1207},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Animal modelling of traumatic brain injury in preclinical drug development : where do we go from here?},
  url          = {http://dx.doi.org/10.1111/j.1476-5381.2010.01163.x},
  volume       = {164},
  year         = {2011},
}