Neuroprotective actions of FK506 and cyclosporin A on motor neuron survival following neonatal axotomy.
We show that nonimmunosuppressive analogues of the immunosuppressive drugs FK506 and cyclosporin A (CsA) rescue axotomized neonatal motor neuron death. Unilateral sciatic nerve was transected in neonatal rats. Animals were then treated daily with different doses of FK506 and CsA for 14 days with intraperitoneal injection. Control rats received phosphate buffer saline (PBS) in the same fashion. After treatment, the number of spinal motor neurons was determined at L4 level. In comparison with vehicle, both FK506 (5.0 mg kg(-1)) and CsA (10.0 mg kg(-1)) rescued motor neuron death in a similar way. These results indicate therapeutic relevance in the treatment of damaged motor neuron disorders, such as motor neuropathy or amyotrophic lateral sclerosis.
Iwasaki
Yasuo
Y
The Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan. yaso@med.toho-u.ac.jp
Ichikawa
Yasumitsu
Y
Igarashi
Osamu
O
Iwamoto
Kounosuke
K
Kinoshitata
Masao
M
Ikeda
Ken
K
D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D016923:Cell Death; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology*
D018696:Neuroprotective Agents; D016572:Cyclosporine; D016559:Tacrolimus