RESUMEN
Immunobiologicals are a reality in current clinical practice and have increasingly gained space in the inflammatory disease scenario, especially in dermatology, with approved drugs for psoriasis, atopic dermatitis, and hidradenitis suppurativa, in addition to many others undergoing study. It is important for dermatologists to have knowledge of the medications approved in Brazil, for the best management of dermatoses, in addition to the fact that they represent hope for improvement in patients with chronic diseases.
Asunto(s)
Dermatitis Atópica , Dermatología , Hidradenitis Supurativa , Psoriasis , Brasil , Dermatitis Atópica/tratamiento farmacológico , Hidradenitis Supurativa/tratamiento farmacológico , Humanos , Psoriasis/tratamiento farmacológicoRESUMEN
Focal cortical dysplasia is a highly epileptogenic cortical malformation with few treatment options. Here, we generated human cortical organoids from patients with focal cortical dysplasia type II. Using this human model, we mimicked some focal cortical dysplasia hallmarks, such as impaired cell proliferation, the presence of dysmorphic neurons and balloon cells, and neuronal network hyperexcitability. Furthermore, we observed alterations in the adherens junctions zonula occludens-1 and partitioning defective 3, reduced polarization of the actin cytoskeleton, and fewer synaptic puncta. Focal cortical dysplasia cortical organoids showed downregulation of the small GTPase RHOA, a finding that was confirmed in brain tissue resected from these patients. Functionally, both spontaneous and optogenetically-evoked electrical activity revealed hyperexcitability and enhanced network connectivity in focal cortical dysplasia organoids. Taken together, our findings suggest a ventricular zone instability in tissue cohesion of neuroepithelial cells, leading to a maturational arrest of progenitors or newborn neurons, which may predispose to cellular and functional immaturity and compromise the formation of neural networks in focal cortical dysplasia.
Asunto(s)
Epilepsia , Malformaciones del Desarrollo Cortical de Grupo I , Malformaciones del Desarrollo Cortical , Encéfalo , Humanos , Recién Nacido , NeuronasRESUMEN
Abstract Immunobiologicals are a reality in current clinical practice and have increasingly gained space in the inflammatory disease scenario, especially in dermatology, with approved drugs for psoriasis, atopic dermatitis, and hidradenitis suppurativa, in addition to many others undergoing study. It is important for dermatologists to have knowledge of the medications approved in Brazil, for the best management of dermatoses, in addition to the fact that they represent hope for improvement in patients with chronic diseases.