Figure 2

Intracerebroventricular si-InR, si-IGF-1R, or si-IGF-2R impairs cerebellar development. Cerebella of rats treated by intracerebroventricular (ICV) injection of si-RNA targeting (A,E,I) nonspecific sequences (Scr), (B,F,J) InR, (C,G,K) IGF-1R, or (D,H,L) IGF-2R, were harvested on (A-H) P9 or (I-L) P20, sectioned in the mid-sagittal plane, fixed in Histochoice, and embedded in paraffin. Histological sections were stained with Hematoxylin and Eosin. Photographs were taken at magnifications of (A-D) 100×, (E-H) 200×, or (I-L) 40×. (B-D) Note relative simplification of the folia and variability in the thickness of the cortex, (D, H) reduced compactness and cellularity within the internal granule cell layer, and (B-D, F-H) impaired development of white matter (wm) with (B,F,D,H) increased gliosis or (C,G) markedly reduced parenchymal volume and appearance of cavitation one week after the ICV injections of si-Inr, si-IGF-1R, or si-IGF-2R relative to si-Scr controls (A,E). (I-L) In P20 rats, the structural differences in cerebellar architecture caused by the si-RNA treatments were more subtle and mainly manifested by slightly more irregular and shallow folia in (J) si-InR and (L) si-IGF-2R treated relative to (I) si-Scr controls. Abbreviations: igl = internal granule cell layer; egl = external granule cell layer; pcl = Purkinje cell layer; wm = white matter; ml = molecular layer.