Cognitive dysfunction after experimental febrile seizures.
While the majority of children with febrile seizures have an excellent prognosis, a small percentage are later discovered to have cognitive impairment. Whether the febrile seizures produce the cognitive deficits or the febrile seizures are a marker or the result of underlying brain pathology is not clear from the clinical literature. We evaluated hippocampal and prefrontal cortex function in adult rats with a prior history of experimental febrile seizures as rat pups. All of the rat pups had MRI brain scans following the seizures. Rats subjected to experimental febrile seizures were found to have moderate deficits in working and reference memory and strategy shifting in the Morris water maze test. A possible basis for these hippocampal deficits involved abnormal firing rate and poor stability of hippocampal CA1 place cells, neurons involved in encoding and retrieval of spatial information. Additional derangements of interneuron firing in the CA1 hippocampal circuit suggested a complex network dysfunction in the rats. MRI T2 values in the hippocampus were significantly elevated in 50% of seizure-experiencing rats. Learning and memory functions of these T2-positive rats were significantly worse than those of T2-negative cohorts and of controls. We conclude that cognitive dysfunction involving the hippocampus and prefrontal cortex networks occur following experimental febrile seizures and that the MRI provides a potential biomarker for hippocampal deficits in a model of prolonged human febrile seizures.
Dubé
Céline M
CM
Department of Pediatrics, ZOT 4475, University of California, Irvine 92697-4475, USA.
Zhou
Jun-Li
JL
Hamamura
Mark
M
Zhao
Qian
Q
Ring
Alex
A
Abrahams
Jennifer
J
McIntyre
Katherine
K
Nalcioglu
Orhan
O
Shatskih
Tatiana
T
Baram
Tallie Z
TZ
Holmes
Gregory L
GL
D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D003294:Seizures, Febrile / Q000150:complications*; D013028:Space Perception / Q000502:physiology