There is a high incidence of epilepsy in patients with polymicrogyria; however, the epileptogenic mechanisms are largely unknown. The density of parvalbumin-immunoreactive interneurons was evaluated in an experimental model of polymicrogyria, in order to assess the potential changes in the development of one population of inhibitory interneurons. Newborn hamsters received an intracerebral injection of ibotenate, and all injected animals showed abnormal cortical layers characterized by one or two microgyrus in the fronto-parietal cortex. A quantitative analysis revealed that the ratios of parvalbumin-immunoreactive neurons in total neurons were significantly reduced in the medial paramicrogyral area, and in the medial and central parts of microgyrus in comparison to that in the lateral part of microgyrus (P<0.01). The lateral paramicrogyral area had the greatest number of parvalbumin-immunoreactive neurons, which was increased significantly in comparison to that in the control cortex (P<0.01). We suggest that the callosal, thalamic and intracortical afferents to the microgyrus and paramicrogyral area may induce a remarkable imbalance between the excitatory and inhibitory activities of the cortical structures, associated with the epileptogenic mechanism in polymicrogyria.
"Akakin and colleagues (2012) found both parvalbumin-containing and somatostatin-containing interneurons were reduced in newborn rats with focal cortical dysplasia following exposure to intrauterine radiation. Similar results were reported by Takano (2012) who produced examined areas of polymicrogyria in neonatal hamsters injected intracortically with ibotenic acid which causes excitotoxic cell death and a resulting dysplasia. Parvalbumin containing interneurons were significantly reduced in and around the area of polymicrogyria. "
[Show abstract][Hide abstract] ABSTRACT: The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype.
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