| Co-Investigator(Kenkyū-buntansha) |
OI Shizuo Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (30194062)
HIDAKA Mitsuru Tokai University, School of Medicine, Assistant Researcher, 医学部, 助手 (90256123)
TANAKA Yoshimi Tokai University, School of Medicine, Assistant Researcher, 医学部, 助手 (20227193)
TSUGANE Ryuichi Tokai University, School of Medicine, Professor, 医学部, 教授 (70022902)
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| Research Abstract |
In studying hydrocephalus, many authors have been concerned with the ependymal, subependymal and/or cortical pathological changes. Some authors have also brought attention to changes in deep brain structures, e.g, loss of dendritic spines in hippocampus, reactive astrogliosis in the deep cortical layers. At the neurotransmitter level, there have been many reports concerning disturbances of serotoninergic, dopaminergic, noradrenergic as well as muscarinic cholinergic systems in experimental hydrocephalus.
The neurotrophin family includes nerve growth factor (NGF, Levi-Montalcini 1968), brain derived neurotrophic factor (BDNF) (Barde, 1982), neurotrophin-3 (NT3) (various, 1990), neurotrophin-4/5 (NT-4/5) (Hallbook, 1991), neurotrophin-6 (NT-6) (Gotz, 1994) and neurotrophin-7 (NT-7)(Nilsson, 1998). It may exert both local effects and act as a target-derived trophic factor in multiple systems. There are two types of receptors for the neurotrophins, the low affinity neurotrophin receptor (LA
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NR), to which all neurotrophins are able to bind, and factor-specific high affinity receptors belonging to the Trk family. NGF binds to Trk, BDNF to TrkB, NT-3 to TrkC, and NT-4 to TrkB.
The aims and results of this project were, 1. To monitor possible changes in the CNS tissures for neurotrophins and their high affinity receptors in kaolin-induced hydrocephalus. Neurotrophin mRNAs were upregulated that NGF in corpus callosum, the medial septal nucleus and the striatum, BDNF in the hippocampus, NT-3 in the hippocampus and corpus callosum, trkB in the hippocampus, and trkC in the hippocampus and corpus callosum. (Nerv Syst Child 1998, INT-7 meeting 1999. Exp Neurol (Suppl) in press). 2. To know the pathological changes of kaolin induced syringo/hydromyelic model. The results showed the reactive microglial and NGF IR positive astroglial proliferation in the dorsal spinal cord. (ISPN meeting 1998, JSPN meeting 1998). 3. To know the immunological reactions of neurotrophin family (NGF, BDNF and NT-3) and GDNF. At 2 weeks after the NT-3 and GDNF injected into the striatum, reactive microglial proliferation wers examined at the cholinergic bundles in the striatum (JSNGRT Meeting 1998). 4. To know the microglial development in the perinatal periods, which is concerned with or without developmental neuronal cell death. Mature microglial marker was positive at the deliverly, but not in the early periods in the cortex.(Nerv Syst Child 1999). 5. To know the microglial reactions in the traumatic brain injury (TBI) and the neuroprotection effects of immunosuppressant. FK 506 reduced the reactive astro- and micro-glioses in the model of TBI. (JSNGRT Meeting 1999). 6. Following the results of project No.1, NT-3 intraventricular administration was performed. The results showed reduction of numbers of reactive microglia in the white matter, but not significant (JSPN Meeting 1999). 7. NGr intraventricular administration has performed, however, the results have not been coming yet. Less
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