A selective depolarisation-induced increase in excitatory amino acid neurotransmitter release in rat medial prefrontal cortex using a microdialysis model of traumatic brain injury

Smyth, Aoife; Gilchrist, Michael D.; O’Connor, William T.

Affiliations

¹Applied Neurotherapeutics Research Group, Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

²Department of Mechanical Engineering, University College Dublin, Ireland

Abstract and keywords

This 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) impact 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. This finding may in part explain the excitotoxicity that contributes to diffuse posttraumatic lesions associated with secondary injury.

Keywords: glutamate, GABA, KCl, HPLC, rat, basal, stimulated levels

Links

DOI: 10.1007/1-4020-3796-1_41

Cited Works (1)

Year	Entry
1991	Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL. A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Meth. October 1991;39(3):253-262.