Imaging the Neural Substrates Involved in the Genesis of Pentylenetetrazol‐induced Seizures

• Published in: Epilepsia (Copenhagen) Vol. 47; no. 4; pp. 745 - 754
• Main Authors: Brevard, Mathew E., Kulkarni, Praveen, King, Jean A., Ferris, Craig F.
• Format: Journal Article
• Language: English
• Published: 350 Main Street , Malden , MA 02148 , USA and 9600 Garsington Road , Oxford , OX4 2XG , England Blackwell Publishing Inc 01.04.2006; Blackwell
• Subjects: Animals; Anterior thalamus; Biological and medical sciences; BOLD technique; Brain Mapping; Dentate gyrus; Dentate Gyrus - physiopathology; Disease Models, Animal; Electroencephalography - statistics & numerical data; Epilepsy, Absence - chemically induced; Epilepsy, Absence - physiopathology; Ethosuximide; Ethosuximide - pharmacology; Functional MRI; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - physiopathology; Human viral diseases; Infectious diseases; Investigative techniques, diagnostic techniques (general aspects); Magnetic Resonance Imaging - statistics & numerical data; Male; Medical sciences; Nervous system; Nervous system (semeiology, syndromes); Neural Pathways - metabolism; Neural Pathways - physiopathology; Neurology; Oxygen - blood; Pentylenetetrazol; Pentylenetetrazole; Pilot Projects; Prosencephalon - metabolism; Prosencephalon - physiopathology; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Rats; Rats, Sprague-Dawley; Retrosplenial cortex; Seizures - chemically induced; Seizures - physiopathology; Seizures - prevention & control; Thalamic Nuclei - physiopathology; Thalamus - physiopathology; Viral diseases; Viral diseases of the nervous system; Nervous system diseases; Ethosuximide; Epilepsy; Central nervous system; BOLD technique- Functional MRI-Anterior thalamus-Retrosplenial cortex- Dentate gyrus-Pentylenetetrazol-Ethosuximide; Anticonvulsant; Epilepsy provoked by; Nuclear magnetic resonance imaging; Cerebral disorder; Dentate gyrus; Central nervous system disease; Thalamus; Technique; Hippocampus
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2006.00502.x

Purpose: 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 ∼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 ∼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.