A novel approach for imaging brain-behavior relationships in mice reveals unexpected metabolic patterns during seizures in the absence of tissue plasminogen activator.
Medically refractory seizures cause inflammation and neurodegeneration. Seizure initiation thresholds have been linked in mice to the serine protease tissue plasminogen activator (tPA); mice lacking tPA exhibit resistance to seizure induction, and the ensuing inflammation and neurodegeneration are similarly suppressed. Seizure foci in humans can be examined using PET employing 2-deoxy-2[(18)F]fluoro-d-glucose ((18)FDG) as a tracer to visualize metabolic dysfunction. However, there currently exist no such methods in mice to correlate measures of brain activation with behavior. Using a novel method for small animal PET data analysis, we examine patterns of (18)FDG uptake in wild-type and tPA(-/-) mice and find that they correlate with the severity of drug-induced seizure initiation. Furthermore, we report unexpected activations that may underlie the tPA modulation of seizure susceptibility. The methods described here should be applicable to other mouse models of human neurological disease.
Mirrione
Martine M
MM
Graduate Program in Molecular and Cellular Pharmacology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Schiffer
Wynne K
WK
Fowler
Joanna S
JS
Alexoff
Dave L
DL
Dewey
Stephen L
SL
Tsirka
Stella E
SE
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D018345:Mice, Knockout; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012640:Seizures / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D010959:Tissue Plasminogen Activator
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