Pathophysiological mechanisms underlying the development of focal cortical dysplasia and their association with epilepsy: Experimental models as a research approach

Abstract

Focal cortical dysplasia (FCD) is a structural lesion that is the most common anatomical lesion identified in children, and the second most common in adults with drug-resistant focal-onset epilepsy. These lesions vary in size, location, and histopathological manifestations. FCDs are classified into three subtypes associated with loss-of-function mutations in PI3K/AKT, TSC1/TSC2, RHEB, and DEPDC/NPRL2/NPRL3. During the decades of research into FCD, experimental models have played an irreplaceable role in the research design of studies investigating disease pathogenesis, pathophysiology, and treatment. Further, the establishment of FCD experimental models has moved the field forward by (1) revealing the cellular processes and signaling pathways underlying FCD pathogenesis and (2) varying the methods and materials to study the function of FCD proteins. Currently, FCD experimental models are predominantly murine, with each model providing unique insights into FCD lesions. This review briefly summarizes the pathology and molecular functions of FCD, further comparing the available modeling methods and indexes, as well as the utilization of models, followed by an analysis of the similarities, advantages, and disadvantages between these models and human FCD.