| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
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| Research Abstract |
We hypothesized that an immunological reaction plays a role in the development of vasospasm afer subarachnoid hemorrhage (SAH). Under this hypothesis, we had investigated the therapeutic effect of cyclosporine for vasospasm, and obtained a favorable result. To testify this hypothesis further, we used a new potent immunosuppressant, FK-506, for vasospasm. We also examined chronological changes of serum compliments (C_3, CH_<50>). After sacrificing an animal, we checked pharmachological effect of FK-506 on K^+-dependent and protein kinase C (PKC)-dependent contarctions. Furthermore, we investigated immunoglobulin deposition in the arterial wall by immunohistochemistry. Dogs were classified into four groups, sham (saline injected), SAH (two-hemorrhage model), FK-506-treated I (0.15mg/kg i.m.) and-treated II (0.3mg/kg i.m.) groups. Angiograms showed severe vasospasm in SAH,treated I and ll, and no significant difference was observed among these three groups. Serum compliments did not show any significant changes in four guoups. FK-506 did not show any vasodilatory effects on K^+-dependent and PKC-dependent contarctions. Because of technical problems, we did not succeed in staining any immunoglobulin depositions in arterial walls in any group.
Contrary to our expectation, FK-506 did not show any therapeutic effect on vasospasm after SAH.There is a significant discepancy between cyclosporine and FK-506 regarding therapeutic effect on vasospasm. We speculated that this difference might be based on the pnarmacological difference of immunosuppression between the two, especially the mechanism of suppression on the production of interleukine 2. If we could have a chance to investigate this point, a pathogenensis of vasospasm could be clarified further.
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