Epileptogenesis during development: injury, circuit recruitment, and plasticity.
OBJECTIVE
To use animal models of variable seizure induction in rats at different developmental stages to determine contributing factors for spontaneous seizures resulting from status epilepticus (SE) early in life.


METHODS
Two models of SE with distinct modes of seizure induction, lithium-pilocarpine (LiPC) and perforant path stimulation (PPS), were used at different ages. Multiple methods of determining neurodegeneration during an acute period and plastic changes in those monitored during the chronic phase were used.


RESULTS
Different modes of seizure induction lead to varying types and extents of damage, dependent on the age of the animals at the time of insult. LiPC resulted in injury to animals as young as 2 weeks and became widespread in animals 3 weeks old, whereas widespread damage after PPS was not seen until P35. Rats at an age with widespread damage in response to seizures also showed extensive immediate-early gene activation and often developed spontaneous seizures and features of hippocampal plasticity seen in the epileptic brain.


CONCLUSIONS
SE early in life results in multiple consequences to the developing brain. These changes, coexisting in the nonepileptic brain, can overlap in a maladaptive combination to result in the diseased state of epilepsy. The consequence of early seizures in immature animals is a function of both the developmental stage and the method of seizure induction.
Department of Pediatrics, 22-474 MDCC, UCLA School of Medicine, Los Angeles, CA 90095, USA. RSankar@ucla.edu
Raman
R
Sankar
Don
D
Shin
Hantao
H
Liu
Claude
C
Wasterlain
Andrey
A
Mazarati
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D003292:Convulsants; D018891:Dentate Gyrus / Q000503:physiopathology; D004558:Electric Stimulation; D006624:Hippocampus / Q000473:pathology; D007150:Immunohistochemistry; D008094:Lithium; D019599:Mossy Fibers, Hippocampal / Q000503:physiopathology; D009433:Neural Inhibition; D009434:Neural Pathways / Q000503:physiopathology; D009473:Neuronal Plasticity; D019580:Perforant Pathway; D010751:Phosphopyruvate Hydratase / Q000097:blood; D010862:Pilocarpine; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011999:Recruitment, Neurophysiological; D013226:Status Epilepticus / Q000139:chemically induced* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D013373:Substance P / Q000378:metabolism
D003292:Convulsants; D016755:Proto-Oncogene Proteins c-jun; D010862:Pilocarpine; D013373:Substance P; D008094:Lithium; D010751:Phosphopyruvate Hydratase