FK506 Itself Does Not Demonstrate Neurotoxicity in the Mouse Brain

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We examined histochemical changes in Nissl's staining, glial fibrillary acidic protein (GFAP)- and myelin basic protein (MBP)-immunoreactive cell bodies and fibers in mouse brains after intraperitoneal or intraventricular injection of FK506 (tacrolimus, Prograf^<(R)>). After intraperitoneal injection of FK506, there were no marked changes in either GFAP- and MBP-immunohistochemical staining or Nissl's staining. After intraventricular injection, there were no marked changes in either MBP-immunohistochemical staining or Nissl's staining, but extensive increases in GFAP-immunoreactive cell bodies and the densities of GFAP-immunoreactive fibers were detected in the olfactory tubercle, caudate putamen, hippocampus and neo-cortex. In this study, there were no statistically significant differences in GFAP-immunoreactive cell bodies, or the densities of GFAP-immunoreactive fibers between the FK506 injected group and placebo group. These results suggest that FK506 itself does not demonstrate neurotoxicity. However various factors such as vasoconstriction appear under various conditions, such as GVHD or infection in vivo, especially after organ transplantation. Therefore, it can be said that not only FK506, but also various other factors are involved in neurotoxicity and FK506-related leukoencephalopathy.
日本組織細胞化学会の論文