1989 Fiscal Year Final Research Report Summary
EXPERIMENTAL STUDY FOR NEURONAL MIGRATION DISORDERS DUE TO BARRIER DEFECTS OF THE PIAL-GLIAL BORDER: INTENTION OF ANIMAL MODEL CONFIRMATION OF THE BRAIN MALFORMATIONS IN FUKUYAMA CONGENITAL MUSCULAR DYSTROPHY
| Project/Area Number |
63570437
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOTTORI UNIVERSITY |
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Principal Investigator |
TAKADA Kuniyasu DEPARTMENT OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (00105909)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Hitoshi DEPARTMENT OF MEDICINE, ASSISTANT, 医学部・附属病院, 助手 (00186123)
HOUDOU Sadataka NATIONAL INSTITUTE OF NEUROSCIENCE, NCNP, RESEARCH FELLOW, 神経センター神経研究所疾病研究第二部, 非常勤流動研究員 (70192317)
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| Project Period (FY) |
1988 – 1989
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| Keywords | FUKUYAMA CONGENITAL MUSCULAR DYSTROPHY / CEREBRAL CORTEX, ABNORMALITIES / FETAL PERIOD / MIGRATION OF NEURONAL CELLS / PIAL-GLIAL BARRIER / PIA MATER |
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| Research Abstract |
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
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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
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