|Budget Amount *help
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥900,000 (Direct Cost: ¥900,000)
In order to make clear the pathogenesis of the unique cerebral malformation in Fukuyama type congenital muscular dystrophy (FCMD) according to our own hypothesis based on neuropathological observations, experiments are planned to induce in newborn or late fetal rodents glio-mesenchymal proliferation in the subarachnnoidal spaces and focal defects of pial-glial (or leptomeningo- glioneural) barriers, and subsequently similar migration disorders in FCMD. Human autopsy materials of FCMD including a fetal case are also reevaluated neuropathologically.
At first we intended focal cold injuries in the newborn rat cerebrum, because migration disorders are often concomitant in the cortex around the human porencephalic cysts. Although focal cortical defects similar to human porencephaly were induced, gyral or cytoarchitectural abnormalities were unsuccessful. In the next step, we try to induce cerebellar dysplasia (micropoly- gyria) by intracisternal administration to newborn rats of a neurotoxic
agent, 6-hydroxydopamine, by which some investigators have succeeded to induce abnormal cerebellar cortex. In our experiment, focal meningeal thicking and hydrocephalus were induced in a few cases, but true cerebellar cortical dysplaga has not been made. The experiment is still continued.
Human autopsy cases were reevaluated by a Golgi and angioarchitectural study. the results suggested that in the loci with minor dysplasia, abnormal neural accumulation is mainly formed around long penetrating vessels, while in the severest malformation the cerebral cortex also consisted of two heterogeneous layers; a supportive finding of massive accumulation of migrating neurons in the thickened glio-mesenchymal layer.
Analysis of fetal cerebellar cortex suggested that, although mesenchymal proliferation in the fetal period is important as well as in the cerebral cortex, but interruption of cortical components including precursors of granular or Purkinje cells by proliferated mesencynal tissue is rather essential for development of cerebellar cortical dysplasia, instead of glial-mesenchymal intermixing seen in the cerebrum.
Our results obtained from animal experiments are still minimal, but human neuropathological analysis, including fetal case, is significant. We hope to continue to elucidate the pathogenesis of this peculiar brain malformation, which is particularly common in Japan. Less