Severity of histopathologic abnormalities and in vivo epileptogenicity in the in utero radiation model of rats is dose dependent.
OBJECTIVE
Malformations of cortical development (MCDs) are a frequent cause of refractory epilepsy in humans. The in utero radiation model in rats shares many clinical and histopathologic characteristics with human MCDs. Previous studies reported the presence of clinical seizures in radiated rats, but also suggested a dose-dependent differential effect.


METHODS
Time-pregnant Sprague-Dawley rats were irradiated on embryonic day E17 with 100 cGy (low dose), 145 cGy (medium dose), 175 cGy (high dose), or were left untreated. Their adult litters were implanted with bifrontal epidural and hippocampal depth electrodes and underwent long-term video-EEG monitoring. After 2 weeks of monitoring, the animals were killed and their brains processed for histological studies.


RESULTS
Spikes were most frequently found in the rats that were subjected to low- and medium-dose radiation at E17 and were less frequently seen in the animals that were subjected to high-dose radiation. No interictal spikes were found in any of the control animals. Seizures were recorded in three of five animals of the medium-dose group. Histological studies showed a dose-dependent decrease in cortical thickness as well as an increase of cortical and hippocampal disorganization.


CONCLUSIONS
In vivo epileptogenicity in radiated animals was present only in mild or moderate MCD. No in vivo epileptogenicity was seen in severe radiation-induced MCD.
Kellinghaus
Christoph
C
Section of Epilepsy, Department of Neurology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Kunieda
Takeharu
T
Ying
Zhong
Z
Pan
Andrew
A
Lüders
Hans O
HO
Najm
Imad M
IM
D000016:Abnormalities, Radiation-Induced / Q000473:pathology*; D000818:Animals; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004569:Electroencephalography; D004827:Epilepsy / Q000151:congenital / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D005333:Fetus / Q000528:radiation effects*; D006624:Hippocampus / Q000473:pathology / Q000528:radiation effects; D019579:Neocortex / Q000473:pathology / Q000528:radiation effects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley