Seizure susceptibility in immature rats with micrencephaly induced by prenatal exposure to methylazoxymethanol acetate.
The administration of the alkylating neurotoxin methylazoxymethanol acetate (MAM) to pregnant rats on day 15 of gestation induces, in the offspring, a marked micrencephaly, characterized by an impaired formation of interneurons at cortical, hippocampal and striatal levels. Since in man developmental CNS malformations are often associated with severe epileptogenic encephalopathies with seizures appearing in the first months or years of life, we have studied the development of kainic-acid- and bicuculline-induced seizures in 15- and 30-day-old rats, prenatally exposed to MAM. Compared to controls, a higher susceptibility to seizures has been found in micrencephalic rats aged 15 days, while no significant differences have been observed in those aged 30 days. It is hypothesized that the cerebral global anatomical dysgenesis caused by MAM underlies the higher seizure susceptibility shown by animals during the first periods of life. Successively, the processes of adjustment occurring between the cerebral regions affected by the neurotoxic action of MAM and the afferent and efferent pathways spared by the substance may re-establish adequate interneuronal relationships and, therefore, a normal convulsive susceptibility.
de Feo
M R
MR
Department of Neurological Science, La Sapienza University, Rome, Italy.
Mecarelli
O
O
Ricci
G F
GF
D000367:Age Factors; D000818:Animals; D001640:Bicuculline; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000002:abnormalities* / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007608:Kainic Acid; D008431:Maternal-Fetal Exchange; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*
D008746:Methylazoxymethanol Acetate; D007608:Kainic Acid; D001640:Bicuculline