Status epilepticus in 12-day-old rats leads to temporal lobe neurodegeneration and volume reduction: a histologic and MRI study.
OBJECTIVE
Whether status epilepticus (SE) in early infancy, rather than the underlying illness, leads to temporal lobe neurodegeneration and volume reduction remains controversial.


METHODS
SE was induced with LiCl-pilocarpine in P12 rats. To assess acute neuronal damage, brains (five controls, five with SE) were investigated at 8 h after SE by using silver and Fluoro-Jade B staining. Some brains from the early phase were processed for electron microscopy. To assess chronic changes, brains from nine controls and 13 rats with SE at P12 were analyzed after 3 months by using histology and magnetic resonance imaging (MRI).


RESULTS
MRI analysis of the temporal lobe of adult animals with SE at P12 indicated that 23% of the rats had hippocampal, 15% had amygdaloid, and 31% had perirhinal volume reduction. Histologic analysis of sections from the MR-imaged brains correlated with the MRI data. Analysis of neurodegeneration 8 h after SE by using both silver and Fluoro-Jade B staining revealed degenerating neurons located in the same temporal lobe regions as the volume reduction in chronic samples. Electron microscopic analysis revealed irreversible ultrastructural alterations. As with the chronic histologic and MRI findings, interanimal variability was seen in the distribution and severity of acute damage.


CONCLUSIONS
Our data indicate that SE at P12 can cause acute neurodegeneration in the hippocampus as well as in the adjacent temporal lobe. It is likely that acute neuronal death contributes to volume reduction in temporal lobe regions that is detected with MRI in a subpopulation of animals in adulthood.
Nairismägi
Jaak
J
Department of Biomedical NMR, Al Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Pitkänen
Asla
A
Kettunen
Mikko I
MI
Kauppinen
Risto A
RA
Kubova
Hana
H
D000679:Amygdala / Q000187:drug effects / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005452:Fluoresceins; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018021:Lithium Chloride; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D009930:Organic Chemicals; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D016622:Silver Staining; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology*; D013702:Temporal Lobe / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure
D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade; D010862:Pilocarpine; D018021:Lithium Chloride