| Popis: |
The present chapter reviews the methyl-azoxy-methanol acetate (MAM) acquired “lesion” model, that is, experimental animals in which structural and persistent brain abnormalities are induced by prenatal exposition to the neurotoxin MAM. MAM is able to kill actively dividing neuroepithelial cells in a narrow time-window, thus selectively affecting the proliferation of specific neuronal cell populations. Single or double MAM administrations on gestational day 15 are able to induce a severe cerebral hypoplasia with a clear rostro-caudal and medio-lateral gradient. In particular, the double MAM exposure is able to induce periventricular and/or intrahippocampal heterotopia, closely mimicking those observed in human periventricular nodular heterotopia associated with dyslamination of cortical layering, and intracortical ectopic neurons. The hyperexcitability of heterotopic neurons and the abnormal cortico-subcortical circuitry connecting the heterotopia with both hippocampus and neocortex in MAM brain produce an animal prone to seizures. In particular, MAM treated rats display a reduced threshold in vivo to many proconvulsant agents. Further, most of the studies were consistent in reporting an intrinsic medically refractoriness of MAM rats to conventional antiepileptic drugs. All these features make the MAM model a suitable tool for both studying epileptogenesis and elucidating the underlying mechanisms of drug-resistance of the malformed brain. |
