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Smyth, Aoife
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Smyth, Aoife
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Smyth, Aoife
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- PublicationAnimal models of traumatic brain injury : a critical evaluationAnimal 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.
1340Scopus© Citations 151 - PublicationA Selective Depolarisation-Induced Increase in Excitatory Amino Acid Neurotransmitter Release in Rat Medial Prefrontal Cortex Using a Microdialysis Model of Traumatic Brain InjuryThis study describes a microdialysis model that investigates the biochemical response of the brain to non-fatal impact trauma. A controlled cortical impact (mild and severe) was performed to the left medial prefrontal cortex (mPfc) in the isoflurane-anaesthesised rat. This was followed by intracerebral microdialysis whereby a microdialysis probe was implanted into the site of the injury. Changes in dialysate glutamate, aspartate and GABA levels were investigated immediately (i.e. 25 min) and 265 min following a local mild and severe impact to the brain. In addition, the effect of local perfusion with a depolarizing concentration of KCl (100 mM, 20 min) was also investigated 165 min after impact. Dialysate levels measured 25 min after impact (n=14) showed an impactdependent increase in glutamate (6 and 8-fold), aspartate (4 and 5-fold) and GABA (3 and 6-fold) following mild and severe impact respectively compared to non-impact controls. Dialysate levels measured 265 min after mild (n=12) and severe (n=13) impt had stabilized and continued to show a local 5-fold (mild) and 4-fold (severe) increase in local glutamate, a 6-fold (mild) and 3-fold (severe) increase in aspartate and a (3-fold (mild) and 5-fold (severe)) increase in GABA levels compared to control. Intra-mPfc KCl (n=14) increased local dialysate glutamate levels (4-fold following mild impact and 3-fold following severe impact) and aspartate levels (2-fold after both mild and severe impact) while GABA levels did not differ from non-impacted controls following either a mild or severe impact. The present findings show that microdialysis in intact brain can be combined with the controlled cortical impact model to reveal selective impact-dependent and prolonged increases in local dialysate amino acid neurotransmitter levels. Furthermore, we reveal that 165 min following either a mild or severe impact to the left mPfc KCl-stimulated glutamate and aspartate release is abnormally increased while GABA release is not different compared to non-impacted controls. Ths finding may in part explain the excitotoxicity that contributes to diffuse posttraumatic lesions associated with secondary injury.
302Scopus© Citations 2