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The effects of PBN (phenyl-butyl-nitrone) on GLT-1 levels and on the extracellular levels of amino acids and energy metabolites in a model of iron-induced posttraumatic epilepsy.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
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2003 In: Epilepsy Research, ISSN 0920-1211, Vol. 56, no 2-3, 165-173 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 56, no 2-3, 165-173 p.
URN: urn:nbn:se:uu:diva-97025OAI: oai:DiVA.org:uu-97025DiVA: diva2:171793
Available from: 2008-04-10 Created: 2008-04-10Bibliographically approved
In thesis
1. Glutamate Turnover and Energy Metabolism in Brain Injury: Clinical and Experimental Studies
Open this publication in new window or tab >>Glutamate Turnover and Energy Metabolism in Brain Injury: Clinical and Experimental Studies
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During brain activity neurons release the major excitatory transmitter glutamate, which is taken up by astrocytes and converted to glutamine. Glutamine returns to neurons for re-conversion to glutamate. This glutamate-glutamine cycle is energy demanding. Glutamate turnover in injured brain was studied using an animal iron-induced posttraumatic epilepsy model and using neurointensive care data from 33 patients with spontaneous subarachnoid hemorrhage (SAH). Immunoblotting revealed that the functional form of the major astrocytic glutamate uptake protein GLT-1 was decreased 1-5 days following a cortical epileptogenic iron-injection, presumably due to oxidation-induced aggregation. Using microdialysis it was shown that the GLT-1 decrease was associated with increased interstitial glutamate levels and decreased interstitial glutamine levels. The results indicate a possible posttraumatic and post-stroke epileptogenic mechanism. Analysing 3600 microdialysis hours from patients it was found that the interstitial lactate/pyruvate (L/P) ratio correlate with the glutamine/glutamate ratio (r =-0.66). This correlation was as strong as the correlation between L/P and glutamate (r=0.68) and between lactate and glutamate (r=0.65). Pyruvate and glutamine correlated linearly (r=0.52). Energy failure periods, defined as L/P>40, were associated with high interstitial glutamate levels. Glutamine increased or decreased during energy failure periods depending on pyruvate. Energy failure periods were clinically associated with delayed ischemic neurological deficits (DIND) or development of radiologically verified infarcts, confirming that L/P>40 is a pathological microdialysis pattern that can predict ischemic deterioration after SAH. DIND-associated microdialysis patterns were L/P elevations and surges in interstitial glutamine. Glutamine and pyruvate correlated with the cerebral perfusion pressure (r=0.25, r=0.24). Glutamine and the glutamine/glutamate ratio correlated with the intracranial pressure (r=-0.29, r=0.40). Glutamine surges appeared upon substantial lowering of the intracranial pressure by increased cerebrospinal fluid drainage. Increased interstitial glutamine and pyruvate levels may reflect augmented astrocytic glycolysis in recovering brain tissue with increased energy demand due to a high glutamate-glutamine turnover.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 71 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 329
Neurosciences, glutamate, glutamine, lactate, pyruvate, microdialysis, GLT-1, energy metabolism, intracranial pressure, cerebral perfusion pressure, subarachnoid hemorrhage, ischemia, epilepsy, Neurovetenskap
urn:nbn:se:uu:diva-8630 (URN)978-91-554-7155-2 (ISBN)
Public defence
2008-05-02, Rudbecksalen, Rudbecklaboratoriet, Glunten-området, Uppsala Science Park, Dag Hammarskjölds väg 20, Uppsala, 09:15
Available from: 2008-04-10 Created: 2008-04-10Bibliographically approved

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