Hypometabolism precedes limbic atrophy and spontaneous recurrent seizures in a rat model of TLE.
OBJECTIVE
Temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG-PET) is a common finding in patients with drug-resistant temporal lobe epilepsy (TLE). The pathophysiology underlying the hypometabolism, including whether it reflects a primary epileptogenic process, or whether it occurs later as result of limbic atrophy or as a result of chronic seizures, remains unknown. This study aimed to investigate the ontologic relationship among limbic atrophy, histological changes, and hypometabolism in rats.


METHODS
Serial in vivo imaging with FDG-PET and volumetric magnetic resonance imaging (MRI) was acquired before and during the process of limbic epileptogenesis resulting from kainic acid-induced status epilepticus in the rat. The imaging data were correlated with histologic measures of cell loss, and markers of astrogliosis (glial fibrillary acid protein [GFAP]), synaptogenesis (synaptophysin), glucose transporter 1 (Glut1) and energy metabolism (cytochrome oxidase C), on brains of the animals following the final imaging point.


RESULTS
Hippocampal hypometabolism on FDG-PET was found to be present 24 h following status epilepticus, tending to lessen by 1 week and then become more marked again following the onset of spontaneous seizures. Atrophy of limbic structures was evident from 7 days post-SE, becoming progressively more marked on serial MRI over subsequent weeks. No relationship was observed between the severity of MRI-detected atrophy or CA1 pyramidal cell loss and the degree of the hypometabolism on FDG-PET. However, an inverse relationship was observed between hypometabolism and increased expression of the Glut1 and synaptophysin in the hippocampus.


CONCLUSIONS
These findings demonstrate that hypometabolism occurs early in the processes of limbic epileptogenesis and is not merely a consequence of pyramidal cell loss or the progressive atrophy of limbic brain structures that follow. The hypometabolism may reflect cellular mechanisms occurring early during epileptogenesis in addition to any effects of the subsequent recurrent spontaneous seizures.
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
Bianca
B
Jupp
John
J
Williams
David
D
Binns
Rodney J
RJ
Hicks
Lisa
L
Cardamone
Nigel
N
Jones
Sandra
S
Rees
Terence J
TJ
O'Brien
D000704:Analysis of Variance; D000818:Animals; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D001931:Brain Mapping; D056547:CA1 Region, Hippocampal / Q000000981:diagnostic imaging / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004569:Electroencephalography; D003576:Electron Transport Complex IV / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D019788:Fluorodeoxyglucose F18; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D044882:Glucose Metabolism Disorders / Q000209:etiology*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D008032:Limbic System / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D017966:Pyramidal Cells / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D051272:Glucose Transporter Type 1; D016708:Synaptophysin; D019788:Fluorodeoxyglucose F18; D003576:Electron Transport Complex IV; D007608:Kainic Acid