Type

Book Chapter

Authors

William T. O'Connor
M. D. Gilchrist
Aoife Smyth

Subjects

Pharmacology

Topics
kcl rat stimulated levels prefrontal cortex gaba hplc glutamate basal

A Selective Depolarisation-Induced Increase in Excitatory Amino Acid Neurotransmitter Release in Rat Medial Prefrontal Cortex Using a Microdialysis Model of Traumatic Brain Injury (2005)

Abstract 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) 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.
Collections Ireland -> University College Dublin -> Mechanical & Materials Engineering Research Collection
Ireland -> University College Dublin -> College of Engineering & Architecture
Ireland -> University College Dublin -> School of Mechanical and Materials Engineering

Full list of authors on original publication

William T. O'Connor, M. D. Gilchrist, Aoife Smyth

Experts in our system

1
William T. O'Connor
University College Dublin
Total Publications: 21
 
2
M. D. Gilchrist
University College Dublin
Total Publications: 172