2000 Fiscal Year Final Research Report Summary
A neuropathological approach for pathogenesis of onion-bulb formation after acute axonal degeneration in an animal model.
| Project/Area Number |
11670624
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
YOSHIKAWA Hiroo Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90273680)
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| Project Period (FY) |
1999 – 2000
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| Keywords | MSR-A / oxidized phosphatidylcholine / onion-bulb formation / axonal degeneration / compression / isoniazid intoxication |
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| Research Abstract |
To investigate the role of the MSR in myelin phagocytosis in vivo, (1) we produced a single compression lesion to sciatic nerves of both wild-type and MSR class A (MSR-A) knockout (ko) mice, (2) we intoxicated ko mice with isoniazid (INH), and examined the nerves 21 days after compression or intoxication. A morphometric study showed that the average densities of remaining myelinated fibers in wild-type mice and MSR-A ko mice were reduced from about 22000/mm^22 without compression to 7500-10000/mm^2 after compression, with no significant difference between the wild-type and ko mice. The most prominent pathological feature at the compression site was formation of many small onion-bulbs (OBs) in the MSR-A ko mice, whereas the wild-type mice showed only few. With an antibody against oxidized phosphatidylcholine, myelin and its debris in and around compressed nerve fibers were more densely stained in the ko mice than in the wild-type mice, although non-compressed nerve fibers were not stained at all. Foamy cells were identified more in the ko mouse as compared to the wild-type mouse. After INH intoxication, some of the ko mice showed similar changes in their sciatic nerves as in the compression, although immunohistochemical staining with anti-oxidized phosphatidylcholine antibody showed more diffusely stained endoneurium. From these results, we conclude that 1) oxidized phospholipids was generated from the myelin sheath after a nerve compression and INH intoxication, 2) the MSR might have played an important role in scavenging damaged cell membranes including the myelin aheath, and 3) dysfunction of the MSR was responsible for OB formation.
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Research Products
(4 results)
