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Rezaie, P.; Steinbrecher, A.; Briese, M.; Stoltenburg-Didinger, G. and Ulfig, N.
(2004).
Abstract
Type-II lissencephaly (LIS-II) is a rare developmental disorder characterized by the excessive migration of neurons and glia, which breach the glia limitans and accumulate within the subarachnoid space. The cortical structure is completely disrupted, the meninges are thickened, and the surface of the brain presents with a ‘cobblestone-like’ appearance. LIS-II is found in Walker–Warburg syndrome (WWS), muscle–eye–brain disease (MEB) and Fukuyama congenital muscular dystrophy (FCMD), autosomal recessive disorders all of which share features of congenital muscular dystrophy and ocular malformation. Genetic studies have found that abnormal protein glycosylation accounts at least partially, towards disturbances in neuronal migration in LIS-II. Aberrant interactions between neurons, mesenchyme and vasculature are also considered central to the pathogenesis of LIS-II. However, the contribution of glial cell populations towards pathology in LIS-II has not been characterized. Sections of the forebrain from 6 cases (19–31 gestational weeks) all with neuropathological features pathognomonic of LIS-II and WWS were immunoreacted with antisera to detect CD68, MHC-II (for microglia), and GFAP (for astrocytes), and histochemically with RCA-1 and tomato lectins (for microglia and blood vessels). Developing microglia and astrocytes were differentially affected in LIS-II. There was a clear distinction between early microglial maturation (induction of ramified morphology and ‘downregulated’ phenotype in these cells), and degenerative ‘gemistocytic’ changes affecting astrocytes within lower aspects of the cerebral wall. Ramified microglia were aligned with fibre tracts within the intermediate zone and continuing beyond the breach, but absent in neuro-vascular-mesenchymal masses found in upper regions. The lack of microglial activation or evidence of transitory ‘ameboid’ microglia within the telencephalon was quite remarkable, considering the gross abnormalities evident in the upper aspect of the cerebral mantle, and the ‘degenerative changes’ affecting differentiating astrocytes. It is clear that both microglial and astrocyte responses warrant further extensive investigation in relation to the neuronal disturbances found in lissencephaly.
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