Experimental studies on cerebellar foliation. I. A qualitative morphological analysis of cerebellar fissuration defects after neonatal treatment with 6‐OHDA in the rat

Abstract

The present report describes the natural history of defective cerebellar fissuration in the rat after neonatal treatment with 6-hydroxydopamine (6-OHDA). Within 24 hours after an intracisternal (IC) injection of 100 micrograms 6-OHDA cerebellar pial fibroblasts degenerated almost completely and were phagocytosed b macrophages within 2-5 days postinjection (dpi) leaving the cerebellar surface denuded of pia. Bergmann glia end feet at first exhibited morphological signs of gliosis and later formed new sprouts that penetrated the basal lamina and grew into the subarachnoid space covering regenerating pial fibroblasts and also invading ectopic colonies of external granular layer (EGL) cells. Breaches in the basal lamina appeared after the pial fibroblast had been destroyed and were confined to areas where Bergmann glia end feet were absent and where EGL cells were opposed to the basal lamina. EGL cells escaped through these fractures into the subarachnoid space in the fissures, where they proliferated to form large colonies of granule and stellate cells. In those fissures in which EGL ectopia featured, opposing folia fused and fissures were lost. These findings suggest that pial fibroblasts and the basal lamina have an important role in maintaining lobular partition during development of the cerebellum, in establishing cerebellar fissures, and in consolidating Bergmann glia-EGL cell relationships as a prerequisite for orderly migration of EGL cells.

Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum

“…One possibility is that the early expression of genes in AP stripes, such as En1, En2, Pax2, Wnt7b (Millen et al, 1995) and Epha4 (Karam et al, 2000), provides positional clues for the orientation of gcp cell division. Another is that mechanical constraints are conferred through adhesion processes (Blaess et al, 2004;Sievers et al, 1981). Of possible relevance, Gap43, an actin-binding phosphoprotein, has been proposed to provide a link between the orientation of the mitotic spindle of gcps and extrinsic cues, as gcps lacking Gap43 have an altered orientation of mitotic spindles and more frequent horizontal than vertical divisions .…”

Discoidin domain receptor 1 functions in axon extension of cerebellar granule neurons

“…Electron microscopic studies demonstrated that cells in the outer EGL maintain close contacts with the pia (Hausmann and Sievers 1985). Studies in which the drug 6-hydroxydopamine (6-OHDA) has been used to chemically eliminate the pial cells have implicated the pia as playing a role in cerebellar fissuration, lamination, and granule cell proliferation (Sievers et al 1981;Pehlemann et al 1985). In our coculture system, the pia appears to be important for granule cell neurite extension, with pial collagen and DDR1 in granule cells appearing to play a significant role in this process.…”

Vitamin C Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II

“…The first signs of damage in the cerebellar pial fibroblasts and meningeal cells occurred by 24 hours following application, and macrophage phagocytosis at the site of denuded of pia was present by 2 to 5 days. 29 The chemically induced destruction of meningeal cells destabilizes the basal lamina and glia limitans superficialis, further disorganizing the glial scaffold. 40 Sievers et al 30 described Figure 5.…”

“…Subsequently, the loss of integrity through PBM ruptures leads to the excessive growth of EGL cells, spreading from the Bergmann-glia endfeet into the subarachnoid spaces of cerebellar fissures. 29 As a consequence, this change influences neuronal migration as well as regular fissuration and foliation of the cerebellum. 31,32 Similarly, the weakening and rupturing of PBM in our investigation (Fig.…”