Altered distribution of KCC2 in cortical dysplasia in patients with intractable epilepsy

Purpose: To examine the distribution of KCC2, a neuron-specific K ⁺-Cl^- cotransporter, in human cortical dysplasia (CD). Methods: The immunohistochemical expression of KCC2 was investigated in 18 CD specimens obtained during epilepsy surgery. The histopathologic diagnoses were focal CD (FCD) type I (eight cases), FCD type II (six cases), and hemimegalencephaly (HME; four cases). Tissue sections were immunostained for KCC2 and compared with control sections. Results: In the mature nondysplastic cortex, all the layers showed diffuse neuropil staining for KCC2. The somata were stained much less, although subcortical ectopic neurons displayed dense staining in the cytosol (intrasomatic staining). In FCD type I, the cortex showed neuropil staining for KCC2 with less-stained somata. Aberrant giant pyramidal neurons were also less stained at the soma, whereas immature neurons showed intrasomatic staining. Increased numbers of ectopic neurons with intrasomatic staining were noted in the subcortical white matter. In FCD type II, dysmorphic neurons displayed dense intrasomatic staining with reduced staining of the neighboring neuropils. Balloon cells did not stain for KCC2. Dysmorphic neurons in HME also showed intrasomatic staining. Conclusions: Neurons in CD tissues expressed KCC2. However, the subcellular distribution of KCC2 was altered, which might have affected the ionic homeostasis of Cl ^- and K⁺ involved in epileptic activity within CD tissues.