Animal Models of Traumatic Brain Injury

Kochanek, Patrick M.; Dixon, C. Edward

doi:10.1016/b978-1-4160-5316-3.00330-0

Cited by 2 publications

(1 citation statement)

References 115 publications

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“…The tip of the impactor can have a varying surface either flat or round. The impactor tip is driven at a predetermined velocity, depth of penetration and duration of tissue deformation [58]. In pediatric applications most commonly PND 17 rats have been used with various insult parameters, often at a velocity of 4 m/sec and with a depth ranging generally from 1.5–2.5 mm.…”

Section: Unique Facets Of the Developing Brain—relevance To Pediatricmentioning

confidence: 99%

Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

et al. 2017

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PURPOSE Despite the enormity of the problem and the lack of new therapies, research in the pre-clinical arena specifically using pediatric traumatic brain injury (TBI) models is limited. In this review, some of the key models addressing both the age spectrum of pediatric TBI and its unique injury mechanisms will be highlighted. Four topics will be addressed, namely, 1) unique facets of the developing brain important to TBI model development, 2) a description of some of the most commonly used pre-clinical models of severe pediatric TBI including work in both rodents and large animals, 3) a description of the pediatric models of mild TBI and repetitive mild TBI that are relatively new, and finally 4) a discussion of challenges, gaps and potential future directions to further advance work in pediatric TBI models. METHODS This narrative review on the topic of pediatric TBI models was based on review of PUBMED/Medline along with a synthesis of information on key factors in pre-clinical and clinical developmental brain injury that influence TBI modeling. RESULTS In the contemporary literature, six types of models have been used in rats including weight drop, fluid percussion injury (FPI), impact acceleration, controlled cortical impact (CCI), mechanical shaking, and closed head modifications of CCI. In mice, studies are largely restricted to CCI. In large animals, FPI and rotational injury have been used in piglets and shake injury has also been used in lambs. Most of the studies have been in severe injury models, although more recently studies have begun to explore mild and repetitive mild injuries to study concussion. CONCLUSIONS Given the emerging importance of TBI in infants and children, the morbidity and mortality that is produced, along with its purported link to the development of chronic neurodegenerative diseases, studies in these models merit greater systematic investigations along with consortium type approaches and long-term follow-up to translate new therapies to the bedside.

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Section: Unique Facets Of the Developing Brain—relevance To Pediatricmentioning

confidence: 99%

Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

et al. 2017

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A Critical Review of Anaesthetised Animal Models and Alternatives for Military Research, Testing and Training, with a Focus on Blast Damage, Haemorrhage and Resuscitation

Combes

2013

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Military research, testing, and surgical and resuscitation training, are aimed at mitigating the consequences of warfare and terrorism to armed forces and civilians. Traumatisation and tissue damage due to explosions, and acute loss of blood due to haemorrhage, remain crucial, potentially preventable, causes of battlefield casualties and mortalities. There is also the additional threat from inhalation of chemical and aerosolised biological weapons. The use of anaesthetised animal models, and their respective replacement alternatives, for military purposes — particularly for blast injury, haemorrhaging and resuscitation training — is critically reviewed. Scientific problems with the animal models include the use of crude, uncontrolled and non-standardised methods for traumatisation, an inability to model all key trauma mechanisms, and complex modulating effects of general anaesthesia on target organ physiology. Such effects depend on the anaesthetic and influence the cardiovascular system, respiration, breathing, cerebral haemodynamics, neuroprotection, and the integrity of the blood–brain barrier. Some anaesthetics also bind to the NMDA brain receptor with possible differential consequences in control and anaesthetised animals. There is also some evidence for gender-specific effects. Despite the fact that these issues are widely known, there is little published information on their potential, at best, to complicate data interpretation and, at worst, to invalidate animal models. There is also a paucity of detail on the anaesthesiology used in studies, and this can hinder correct data evaluation. Welfare issues relate mainly to the possibility of acute pain as a side-effect of traumatisation in recovered animals. Moreover, there is the increased potential for animals to suffer when anaesthesia is temporary, and the procedures invasive. These dilemmas can be addressed, however, as a diverse range of replacement approaches exist, including computer and mathematical dynamic modelling of the human body, cadavers, interactive human patient simulators for training, in vitro techniques involving organotypic cultures of target organs, and epidemiological and clinical studies. While the first four of these have long proven useful for developing protective measures and predicting the consequences of trauma, and although many phenomena and their sequelae arising from different forms of trauma in vivo can be induced and reproduced in vitro, non-animal approaches require further development, and their validation and use need to be coordinated and harmonised. Recommendations to these ends are proposed, and the scientific and welfare problems associated with animal models are addressed, with the future focus being on the use of batteries of complementary replacement methods deployed in integrated strategies, and on greater transparency and scientific cooperation.

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Animal Models of Traumatic Brain Injury

Cited by 2 publications

References 115 publications

Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

A Critical Review of Anaesthetised Animal Models and Alternatives for Military Research, Testing and Training, with a Focus on Blast Damage, Haemorrhage and Resuscitation

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