A small dose of the immunosuppressive agent FK506 (tacrolimus) protects peripheral nerve from ischemic fiber degeneration.
The immunosuppressant agent FK506 (tacrolimus) has proven to be neuroprotective against brain ischemia, but there are no data on potential neuroprotective effects of FK506 in peripheral nerve ischemia. We examined the potential effects of two doses of FK506 in protecting peripheral nerve from ischemic fiber degeneration. Ischemia in the left sciatic nerve of the rat was produced by injecting 2 x 10(6) microspheres (14 microm) into the left femoral, hypogastric, and superior gluteal arteries in proportions of 47%, 37%, and 17%, respectively. After embolization, FK506 was injected into the left femoral, hypogastric, and superior gluteal arteries in doses of 9.4, 7.4, and 3.4 microg, respectively, for the high-dose group and 4.7, 3.7, and 1.7 microg, respectively, for the low-dose group. The control rats were injected with saline. FK506 treatment resulted in dramatic behavioral improvement in nerve function, in the number of functioning nerve fibers, and in the salvage of a majority of nerve fibers from ischemic fiber degeneration in a dose-dependent fashion. These results suggest that a small dose of FK506 protects peripheral nerve from ischemic fiber degeneration and that it may have potential in the treatment of ischemic neuropathy.
Kihara
M
M
Department of Neurology, School of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. miki@med.kindai.ac.jp
Kamijo
M
M
Nakasaka
Y
Y
Mitsui
Y
Y
Takahashi
M
M
Schmelzer
J D
JD
D000200:Action Potentials; D000818:Animals; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D009412:Nerve Fibers / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D016559:Tacrolimus / Q000494:pharmacology*; D013979:Tibial Nerve / Q000473:pathology*
D007166:Immunosuppressive Agents; D016559:Tacrolimus