Hippocampal CA1 neuron survival and cytosolic FKBP12, the 12 kDa FK506-binding protein, after ischemia and tacrolimus treatment in gerbils.
To assess the neuroprotective effect of tacrolimus (FK506) in transient forebrain ischemia models in gerbils, 10.0 mg/kg of FK506 was injected intraperitoneally immediately following reperfusion and at intervals of 1, 3, 6, 9, and 12 h after reperfusion. FK506 produced a significant neuroprotective effect for up to 6 h after 5 min of ischemia. Immunoblot and immunohistochemistry revealed that the amount of FKBP12, the 12-kDa FK506-binding protein, in the cytosol remained unchanged until 12 h after reperfusion. Translocation of FKBP12 from the nucleus to the cytosol was not observed until 24 h after reperfusion. Administration of FK506 did not appear to induce the cytosolic increase in FKBP12. In this study, no correlation was apparent between the post-ischemic therapeutic efficacy of FK506 and the post-ischemic changes in the cytosolic FKBP12.
Fumoto
Noriyuki
N
Department of Neurosurgery, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime, Japan. fumotono@m.ehime-u.ac.jp
Nakatsuka
Hiroki
H
Ohta
Shinsuke
S
Kumon
Yoshiaki
Y
Ohnishi
Takanori
T
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000494:pharmacology / Q000627:therapeutic use*
D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins