Ycs. Garrido et al., Mitogen-activated protein kinase is increased in the limbic structures of the rat brain during the early stages of status epilepticus, BRAIN RES B, 47(3), 1998, pp. 223-229
Systemic administration of pilocarpine (PILO) in adult rat produces acute l
imbic seizures leading to states epilepticus. Recent studies have shown the
activation of mitogen-activated protein kinase (MAPK) cascades during expe
rimentally induced seizures. MAPK activation may be triggered by glutamater
gic stimulation and may play a key role in signal transduction pathways, In
the present study, immunocytochemistry was used to analyze the spatiotempo
ral distribution pattern of the MARK protein and its active form (A-MAPK) f
ollowing PILO-induced status epilepticus, MAPK and A-MARK immunoreactivitie
s exhibited different patterns of distribution in the brain of normal and e
pileptic rats. The saline-treated rats, as well as the animals that receive
d PILO but did not evolve to status epilepticus, showed a weak but selectiv
e MAPK immunoreactivity, detected in the hippocampal pyramidal neurons, den
tate gyrus, hilus, CA3, CA1, and entorhinal, piriform, and cingulate cortic
es. A-MARK immunoreactivity was instead observed only in neurites of the CA
3 and hilus and in cells of the entorhinal and piriform cortices, In PILO-t
reated rats, between 30 and 60 min after states epilepticus there was an in
crease of the immunoreactivity to both antibodies, which were differently d
istributed throughout several structures of the limbic system. The immunost
aining showed a slight decrease after 5 h of states epilepticus, However, M
ARK and A-MARK immunopositivities decreased markedly after 12 h of states e
pilepticus, returning almost to the basal expression. These findings are co
nsistent with a spatial and time-dependent MAPK expression in selected limb
ic structures, and its activation could represent an initial trigger for ne
uronal modifications that may take part in the mechanism underlying acute e
pileptogenesis and in longlasting neuropathological changes of the PILO mod
el of epilepsy. (C) 1998 Elsevier Science Inc.