Khan Osaama H, Enno Terry, Del Bigio Marc R
Department of Pathology, University of Manitoba and Manitoba Institute for Child Health, 70 Bannatyne Avenue, Winnipeg, Manitoba R3E 0W3, Canada.
Pediatr Neurosurg. 2003 Dec;39(6):309-13. doi: 10.1159/000075259.
Hydrocephalus causes damage to periventricular axons. Tacrolimus, cyclosporine A (CsA) and calpain inhibitors have been shown to protect axons in rat models of acute traumatic brain injury. We hypothesized that these agents would ameliorate the axon damage and behavioral effects in experimental hydrocephalus. Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. Tests of cognitive and motor function were performed on a weekly basis. In a blinded and randomized manner, tacrolimus (FK506; 3.6 mg/kg body weight) or CsA (10 mg/kg) was administered once daily by subcutaneous injection for 2 weeks, beginning 2 weeks after induction of hydrocephalus. In a separate experiment, calpain inhibitor I (10 mg/kg/day) was administered by continuous subcutaneous infusion. The brains were subjected to histopathological and biochemical analyses after 2 weeks of treatment. There was no statistically significant protection in regard to behavior, brain structure or brain composition in any of the experiments. However, there was biochemical and histological evidence of renal injury following chronic tacrolimus and CsA administration. Calcineurin inhibition does not offer significant protection in this rat model of hydrocephalus.
脑积水会导致脑室周围轴突受损。在急性创伤性脑损伤的大鼠模型中，已证实他克莫司、环孢素A（CsA）和钙蛋白酶抑制剂可保护轴突。我们推测这些药物可改善实验性脑积水中的轴突损伤和行为影响。通过向3周龄大鼠的小脑延髓池注射高岭土诱导脑积水。每周进行认知和运动功能测试。在脑积水诱导2周后，以盲法和随机方式，他克莫司（FK5）06；3.6毫克/千克体重）或CsA（10毫克/千克）通过皮下注射每日给药1次，持续2周。在另一项实验中，钙蛋白酶抑制剂I（10毫克/千克/天）通过皮下持续输注给药。治疗2周后对大脑进行组织病理学和生化分析。在任何实验中，在行为、脑结构或脑成分方面均未观察到具有统计学意义的保护作用。然而，长期给予他克莫司和CsA后，有肾脏损伤的生化和组织学证据。在该大鼠脑积水模型中，抑制钙调神经磷酸酶并不能提供显著的保护作用。
