2004 Fiscal Year Final Research Report Summary
Apototic or necrotic changes in pathogeneseis of cerebral vasospasm after subarachnoid hemorrhage
| Project/Area Number |
15591530
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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 |
Cerebral neurosurgery
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| Research Institution | Ehime University |
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Principal Investigator |
OHUE Shiro Ehime University, University Hospital, Lecturers, 医学部附属病院, 講師 (70213626)
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| Project Period (FY) |
2003 – 2004
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| Keywords | subarachnoid hemorrahge / vasospasm / cerebral vessel / Bcl family / cytochrome c / apotosis / Tunnel / mitochondria |
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| Research Abstract |
Cerebral vasospasm after aubarachnoid hemorrhage (SAH) is a combination of prolonged cntracution and morphological changes of vascular smooth muscle cells. Hoever, the pahogenesis of vasospasm including the relationship between contraction and morphological changes remain unclear. In this study, I investigated the changes for signal tansduction concerninig cell apotosis or necrosis of vascular wall after experimental SAH models.
Rat experimental SAH models were made by single or double injection of autologous blood (0,3ml) into the cisterna magna in male Sprague-Dawely rats. The degree of vasospsm in the model was evaluated by the area of histlogical section oh the arteries. The levels of Bcl-family proteins (Bcll-xL/xS, Bax) and cytochrome c were detected by Western blot analysis. The morphological changes such as apotosis or necrosis of smooth muscle layers in the vessels were evaluated by TUNNEL staining and Western blot analysis of cleavavage of poly (adenosine diphosphate ribose) p
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olymerase (PARP).
The basilar arteries in the double SAH group demonstrated severe prolonged vasospasm from 5 to 10 days after SAH, although those in the single SAH group showed mild vasospasm. The Westren blotting of Bcl family proteins of the arterial wall in the double SAH models revealed that Bcl-xL/xS level was significantly lower from 3 days after SAH, and that Bax levels were significantly higher from 5 days after SAH. However, the results of Western blot analysis of the arteryies in the single SAH models demonstrated no significant changes of Bcl-family proteins after SAH. In the double SAH group, cytochrome c leakage from the mitochondria into the cytosol on 5 days after SAH. TUNNEL-positive cells of the smooth muscle layer of the basilar arteries in double SAH were observed on 7 days after SAH, although those in single SAH were not observed after SAH. The Western blotting analysis with PARP antibody in double SAH models revealed that the 116-kD PARP was cleaved into the 85-kD isoform on 7 days after SAH.
The results indicated that the changes of Bcl-family protein levels in spastic vessels induced leakage of cytochrome c from the mitochondria fraction to the cytosol fraction, and cytochorome c induced the subsequent morphological changes following SAH. Less
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Research Products
(2 results)
