T. Mori et al., FK-506 - A NEW IMMUNOSUPPRESSIVE AGENT, FAILED TO REDUCE CEREBRAL VASOSPASM AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE, Journal of veterinary medical science, 55(4), 1993, pp. 581-586
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.