Seizure incidence varies significantly with age, with seizure susceptibilit
y particularly high during the first few years of life. Of significant conc
ern is what effects do brief, repetitive seizures have on the developing br
ain. We approached this issue by examining the change in seizure threshold,
and related markers of neuronal activity and metabolic activity (c-fos mRN
A and 2-deoxyglucose [2DG]), as a function of repetitive seizure episodes i
n immature and mature rats. Starting on postnatal day 15 (P15) (immature) o
r P60 (adult) rats were given two flurothyl seizures a day for 5 days (nine
or ten seizures). The seizure latency profile. our measure of threshold, i
n immature versus adult rats across the 5-day testing period was different.
In immature rats. threshold for the second seizure on each day was signifi
cantly lower than for the first seizure, suggesting that there was little r
efractoriness after the first seizure of the day. In contrast, the mature a
nimal had a significantly longer threshold latency to the second seizure fo
r the first 3 days of testing. The immature animal was also more likely tha
n the adult to exhibit tonic extension as a feature of the first seizure of
the day. Following repetitive seizures. more regions of the CNS showed c-f
os mRNA expression in the immature animal than adults, suggesting that repe
titive seizures in the immature animal activated a greater percentage of th
e brain. Compared with the effects of a single seizure, repetitive seizures
resulted in less 2DG labeling in most regions of the brain (except the hip
pocampus); in the immature brain this difference was more distinct than in
adults. The consequences of repetitive seizures in the immature animal resu
lts in distinctly different seizure behavior and neuronal activity pattern
(c-fos expression) than that observed in the mature animal. (C) 2001 Publis
hed by Elsevier Science B.V.