Claudio Caccia | PubMed Health

PubMed2006

NMDA receptor composition differs among anatomically diverse malformations of cortical development.

Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.

Adolescent↗

PubMed2005

Schizencephaly: clinical spectrum, epilepsy, and pathogenesis.

After almost 60 years since the original description, we have reviewed the results of the more recent studies on schizencephaly in an attempt to delineate its imaging and clinical spectra of presentation and to point out the still unsettled controversies on its pathogenesis. The clinical picture is mainly based on the presence of motor deficits and mental retardation, but the severity of the clinical picture is extremely variable, mainly related to the size and location of the clefts and to the presence of associated cerebral malformations. By contrast, the outcome of epilepsy, which is present in about half of the cases and drug resistant in a third, is not strictly related to the severity of the malformation. Some clinical and functional magnetic resonance imaging studies have suggested that, beside the features of the anatomic damage, the functional reorganization of a malformed and unaffected cortex is most likely crucial in determining the clinical outcome. Review of the genetic studies and the more recent personal data suggests that the role of the EMX2 gene in schizencephaly, if any, is restricted to a minority of cases, leaving the etiopathogenesis of this brain malformation still a matter of study and debate.

Cerebral Cortex↗