Bcl-2 immunoreactive cells with immature neuronal phenotype exist in the nonepileptic adult human brain

Bcl-2, a cell death suppressor protein, is expressed during brain developme nt but is largely down-regulated in the adult central nervous system. We pr eviously reported strong expression of bcl-2 in small, "oligodendrocyte-lik e" cells (OLC) found in glioneuronal hamartias. These hamartias are microsc opic cell rests found in temporal lobe resections from patients with intrac table epilepsy and are considered a form of cerebral microdysgenesis. Howev er, a causative relationship between these rests and seizures is not clear. We now report the identification, lineage characterization, and postnatal ontogeny of hamartia-like cell rests in temporal lobes of nonepileptic huma ns. Postmortem temporal lobes from 28 patients without history of neurologi c disease (mean age = 53 years; range = 20 to 83 years) were studied. Micro scopic cellular aggregates containing immature-appearing, bcl-2-immunoreact ive cells (BIC) (identical to OLC) were observed in 23 of 28 (82%) temporal lobes from nonepileptic individuals. BIC were strongly immunoreactive for neuronal-specific class III beta tubulin, neuronal nuclear antigen, and MAP -2, but were consistently negative for neurofilament proteins and Ki67. Suc h cells were localized to subventricular regions of the caudal amygdala and often extended into the adjacent subcortical white matter and periamygdalo id cortex. BIC became less abundant with advancing age. These findings sugg est that hamartia-like rests containing immature postmitotic neurons are no rmally present in the human brain and that glioneuronal hamartias may not a lways represent a maldevelopmental lesion associated with epilepsy.