FK-506 - A NEW IMMUNOSUPPRESSIVE AGENT, FAILED TO REDUCE CEREBRAL VASOSPASM AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE

To define the relationship between the immunologic reaction and the pa thogenesis of cerebral vasospasm (VS) following experimental subarachn oid hemorrhage (SAH), we examined the effect of a cell mediated immuno suppressive agent, FK-506, isolated from Streptomyces tsukubaensis, by using the canine SAH model. There was a significant vasoconstriction in the basilar artery in the control group after SAH. This constrictio n, however was not successfully prevented by FK-506 or combination of FK-506 and steroid, since there was no significant difference in the v essel caliber size among these groups. The pathologic approach, accomp anied by immunohistochemistry, could not discriminate the differences in the nature of the lesion between the untreated group and FK-506 tre ated groups, except for slight lymphocytic infiltrations present aroun d the basilar artery of untreated group. Histopathologically, inflamma tory reactions consisting of neutrophils, that were not suppressed by FK-506 treatment, were clearly seen around the spastic vessels in the subarachnoid space. Furthermore, several constrictive changes or degen erative alterations were also observed in the spastic vascular wall. I mmunohistochemically, the deposition of IgG, IgM and C3 Was present in the intima and the luminal side of the smooth muscle layer, and capil lary vessels of the brain stem. It is considered that this deposition was caused by increased vascular permeability in VS. On the basis of t he above findings that the cell mediated immunosuppressive agent, FK-5 06 failed to prevent vasoconstriction or pathologic lesions but lympho cytic infiltrations, it is considered that the cell mediated immunopat hogenesis may play little role in producing VS following SAH.