Animal models of traumatic brain injury: a critical evaluation.
Animal models are necessary to elucidate changes occurring after brain injury and to establish new therapeutic strategies towards a stage where drug efficacy in brain injured patients (against all classes of symptoms) can be predicted. In this review, six established animal models of head trauma, namely fluid percussion, rigid indentation, inertial acceleration, impact acceleration, weight-drop and dynamic cortical deformation are evaluated. While no single animal model is entirely successful in reproducing the complete spectrum of pathological changes observed after injury, the validity of these animal models including face, construct, etiological and construct validity and how the models constitute theories about brain injury is addressed. The various types of injury including contact (direct impact) and non-contact (acceleration/deceleration) and their associated pathologies are described. The neuropathologic classifications of brain injury including primary and secondary, focal and diffuse are discussed. Animal models and their compatibility with microdialysis studies are summarised particularly regarding the role of excitatory and inhibitory amino acid neurotransmitters. This review concludes that the study of neurotransmitter interactions within and between brain regions can facilitate the development of novel compounds targeted to treat those cognitive deficits not limited to a single pharmacological class and may be useful in the investigation of new therapeutic strategies and pharmacological testing for improved treatment for traumatic head injury.
Graduate Entry Medical School and Materials and Surface Science Institute, University of Limerick, Limerick, Ireland. William.oconnor@ul.ie
William T
WT
O'Connor
Aoife
A
Smyth
Michael D
MD
Gilchrist
D000818:Animals; D001930:Brain Injuries / Q000175:diagnosis / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods; D008959:Models, Neurological; D009410:Nerve Degeneration / Q000473:pathology; D054928:Validation Studies as Topic