Zhang F, Richardson P M, Holland D P, Guo Q, Tatton W G
Department of Physiology, University of Toronto, Ontario, Canada.
J Neurosci Res. 1995 Mar 1;40(4):564-70. doi: 10.1002/jnr.490400416.
The application of ciliary neurotrophic factor (CNTF) to the cut ends of transected facial nerves in newborn rats has been reported to reduce the death of facial motoneurons (FMns) axotomized by the transection. Systemically delivered CNTF has been found to cause cachexia in adult mice. We compared the influence of dosage of CNTF and (-)-deprenyl on FMn death, weight loss, and animal survival in rat pups that underwent facial nerve transection at the 14th postnatal day (P14). CNTF was administered by osmotic mini-pumps connected to tubing ending either intrathecally or extrathecally near the craniocervical junction. CNTF caused weight loss and animal death that was similar to the cachexia reported in mice if administered in amounts of 1.1 microgram/day or greater. At the same doses, intrathecal CNTF was more effective than extrathecal CNTF in inducing the cachexia. (-)-Deprenyl did not alter animal survival or weight gain, even at high doses (10 mg/kg every 2 days). Intrathecal CNTF and intraperitoneal (-)-deprenyl, but not extrathecal CNTF, significantly increased the survival of the axotomized FMns. (-)-Deprenyl administered twice daily at 0.01 mg/kg was considerably more effective than CNTF in increasing FMn survival due to the limitation on CNTF dosage caused by the animal death.
据报道,将睫状神经营养因子(CNTF)应用于新生大鼠横断面神经的断端,可减少因横断而轴突切断的面神经运动神经元(FMn)的死亡。已发现全身递送的CNTF会导致成年小鼠恶病质。我们比较了CNTF和(-)-司来吉兰的剂量对出生后第14天(P14)接受面神经横断的幼鼠FMn死亡、体重减轻和动物存活的影响。CNTF通过连接到靠近颅颈交界处鞘内或鞘外的管道的渗透微型泵给药。如果以每天1.1微克或更高的量给药,CNTF会导致体重减轻和动物死亡,这与小鼠中报道的恶病质相似。在相同剂量下,鞘内注射CNTF比鞘外注射CNTF更有效地诱导恶病质。即使在高剂量(每2天10毫克/千克)下,(-)-司来吉兰也不会改变动物的存活或体重增加。鞘内注射CNTF和腹腔注射(-)-司来吉兰,而不是鞘外注射CNTF,显著提高了轴突切断的FMn的存活率。由于动物死亡导致CNTF剂量受限,每天两次以0.01毫克/千克给药的(-)-司来吉兰在提高FMn存活率方面比CNTF有效得多。