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11C-autoradiographic studies of dynamic changes in glial cells and benzodiazepine receptor binding in a model of posttraumatic epilepsy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
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(English)Manuscript (preprint) (Other academic)
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URN: urn:nbn:se:uu:diva-180847OAI: oai:DiVA.org:uu-180847DiVA: diva2:551555
Available from: 2012-09-11 Created: 2012-09-11 Last updated: 2013-01-23
In thesis
1. 11C Molecular Imaging in Focal Epilepsy
Open this publication in new window or tab >>11C Molecular Imaging in Focal Epilepsy
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Epilepsy is a common neurological disease affecting 6 million people in Europe. Early prevention and accurate diagnosis and treatment are of importance to obtain seizure freedom. In this thesis new applications of carbon-11-labelled tracers in PET and autoradiographic studies were explored in focal epilepsy.

Patients with low-grade gliomas often experience epileptic seizures. A retrospective PET-study assessing seizure activity, metabolic rate measured with 11C-methionine and other known prognostic factors was performed in patients with glioma. No correlation was found between seizure activity and uptake of methionine. The presence and termination of early seizures was a favourable prognostic factor.

Activation of the neurokinin-1 (NK1) receptor by substance P (SP) induces epileptic activity. PET with the NK1 receptor antagonist GR205171 was performed in patients with temporal lobe epilepsy (TLE) and healthy controls. In TLE patients an increased NK1 receptor availability was found in both hemispheres, most pronounced in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptors and seizure frequency was observed in ipsilateral medial structures consistent with an intrinsic network using the NK1-SP receptor system for transmission of seizure activity.

The uptake of 18F-fluoro-deoxy-glucose (FDG) is related to cerebral blood flow (CBF). Previously, methods to estimate blood flow from dynamic PET data have been described. A retrospective study was conducted in 15 patients undergoing epilepsy surgery investigation, including PET with 11C-FDG and 11C-Flumazenil (FMZ). The dynamic FMZ dataset and pharmacokinetic modeling with a multilinear reference tissue model were used to determine images of relative CBF. Agreement between data of FDG and CBF was analyzed showing a close association between interictal brain metabolism and relative CBF.

Epilepsy often occurs after traumatic brain injuries. Changes in glia and inhibitory neuronal cells contribute to the chain of events leading to seizures. Autoradiography with 11C-PK11195, 11C-L-deprenyl and 11C-Flumazenil in an animal model of posttraumatic epilepsy studied the temporal and spatial distribution of microglia, astrocytes and GABAergic neurons. Results showed an instant increase in microglial activity that subsequently normalized, a late formation of astrogliosis and an instant and prolonged decease in GABA binding. The model can be used to visualize pathophysiological events during the epileptogenesis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 58 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 814
positron emission tomography, methionine, NK1, substance p, flumazenil, deprenyl, pk11195, phosphoimager, autoradiography, TBI, traumatic brain injury, iron chloride, ferrous chloride
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging
Research subject
Neurology; Radiology
urn:nbn:se:uu:diva-179954 (URN)978-91-554-8475-0 (ISBN)
Public defence
2012-10-26, Enghoff salen, Akademiska sjukhuset, ing 50, bv, Uppsala, 09:15 (English)
Available from: 2012-10-04 Created: 2012-08-27 Last updated: 2013-01-23Bibliographically approved

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