Abnormal maturation of non-dysmorphic neurons in focal cortical dysplasia: Immunohistochemical considerations

Immunohistochemistry of focal cortical dysplasia. In the FCD lesion of Case 15 (type II-A) in Table 1, cortical neurons are distributed at random (A). Large and dysmorphic neurons are mainly observed in the deep area (B). Tuj1-immunopositive premature neurons are within the same distribution of MAP2-immunopositive neurons (B and C). Interestingly, Mash1-immunopositive cells localize in the superficial area (D), whereas Prox1-immunopositive cells are in the deep area and white matter (E). Insets in C, D and E are large magnifications of each rectangular region. Cx, cortex; WM, white matter; A, Klüver–Barrera staining; B, MAP2-immunohistochemistry (IHC); C, Tuj1-IHC; D, Mash1-IHC; E, Prox1-IHC. Scale bar is 500μm.

Immunohistochemistry of neocortices of various malformed and normal developing brains. Normal-looking neuron of focal cortical dysplasia (FCD) expresses MAP2 (A1), Tuj1 (A3), Mash1 (A4) and Prox1 (A5), but not Nestin (A2). In tuberous sclerosis (TSC), MAP2 is expressed (B1) and Tuj1 is faintly positive (B3, arrows), but Nestin, Mash1 and Prox1 are negative (B2, B4, and B5). In early fetus brain, Nestin (C2), Tuj1 (C3), Mash1 (C4, arrows) and Prox1 (C5, arrows) are positive immunoreactivities, whereas MAP2 is negative (C1). In 1-month-old brain, MAP2 (D1) and Tuj1 (D3) are faintly immunostained (arrows), whereas Nestin (D2), Mash1 (D4) and Prox1 (D5) are negative. In childhood, MAP2 (E1) is only immunopositive. Scale bars are 50μm.

Normal-looking neurons in focal cortical dysplasia and their abnormal maturation. MAP2-containing cells have no glial components of astrocyte (A–C) or oligodendrocyte (D–F). MAP2-containing cells have Mash1-immunoreactivities (G–I). Many double-labeled cells with MAP2 and Mash1 are visible (G). Tuj1-containing cells have Mash1-immunoreactivities (J–L, arrows in L). All figures of the superficial area of Case 15 (type II-A) are shown in Table 1. A, D and G, MAP2; B, GFAP; C, merged figure of A and B; E, MBP; F, merged figure of D and E; H and K, Mash1; I, merged figure of G and H; J, Tuj1; L, merged figure of J and K. Scale bars indicate 25μm.

Distribution of immunopositive cells in each subtype.