Imaging the neural substrates involved in the genesis of pentylenetetrazol-induced seizures.
OBJECTIVE
Functional imaging of animal models makes it possible to map the functional neuroanatomy contributing to the genesis of seizures. Pentylenetetrazol (PTZ)-induced seizure in rats, a relevant model of human absence and of generalized tonic-clonic epilepsy, was used to stimulate seizure activity within 30 s of administration while collecting continuous, high-resolution, multislice images at subsecond intervals.


METHODS
Pilot studies were conducted to establish a quick and effective PTZ model for the imaging experiments. PTZ was then used to stimulate seizure activity in rats while collecting multislice functional MRI (fMRI) images from the entire forebrain at 4.7 Tesla. Ethosuximide (ESM) also was used to block seizure activity.


RESULTS
Within 2-4 s of PTZ administration, a rapid increase in blood oxygen level-dependent (BOLD) signal intensity was noted in the thalamus, especially the anterior thalamic nuclei. Activity in the anterior thalamus peaked approximately 15 s before seizure onset and was more than twofold greater than that in all other thalamic areas. The retrosplenial cortex showed a twofold greater increase in activity as compared with other cortical areas, also peaking at approximately 15 s. The dentate gyrus was twice as active as other hippocampal areas but peaked just before seizure onset. Treatment with ESM blocked seizures, decreasing PTZ-induced activation in most forebrain areas. The anterior thalamus and retrosplenial cortex were essentially blocked by pretreatment with ESM.


CONCLUSIONS
The anterior thalamus, retrosplenial cortex, and dentate gyrus show the greatest increases in BOLD signal activity before seizure onset. Neurons in these areas may contribute to the neural network controlling the initiation of generalized tonic-clonic seizure.
Brevard
Mathew E
ME
Center for Comparative Neuroimaging, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. mathew.brevard.umassmed.edu
Kulkarni
Praveen
P
King
Jean A
JA
Ferris
Craig F
CF
D000818:Animals; D001931:Brain Mapping; D018891:Dentate Gyrus / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000706:statistics & numerical data*; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000503:physiopathology; D005013:Ethosuximide / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010433:Pentylenetetrazole; D010865:Pilot Projects; D016548:Prosencephalon / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology* / Q000517:prevention & control; D013787:Thalamic Nuclei / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology
D005013:Ethosuximide; D010100:Oxygen; D010433:Pentylenetetrazole