Ju W Y, Holland D P, Tatton W G
Department of Physiology, University of Toronto, Ontario, Canada.
Exp Neurol. 1994 Apr;126(2):233-46. doi: 10.1006/exnr.1994.1061.
(-)-Deprenyl previously was shown to increase the survival of rat facial motoneurons (FMns) after a loss of muscle-derived trophic support caused by axotomy at Postnatal Day 14 (P14) and to increase reactive astrogliosis after traumatic damage to the adult rat striatum. We estimated reactive astrogliosis in facial nuclei at 1, 3, 7, 14, and 21 days after transection of the facial nerve at P14 by two methods: first, by measuring the relative optical density (OD) of GFAP immunoreaction (GFAP-OD) in the facial nuclei and second by determining the relative area of GFAP immunoreactivity (GFAP-AREA) in the same nuclei. Both measures were taken for multiple immunoreacted sections through the length of each facial nuclei by using a control half section at the same brain stem level taken from an unlesioned, age-matched animal. The experimental and control facial nuclear half sections were coimmunoreacted using the "glued" half brain stem method. The facial nerve transections served to axotomize all of the FMns in the ipsilateral facial nuclei. The numbers of surviving FMns were examined at the same time points as above using counts of Nissl-stained somata from serial sections taken through each facial nucleus. We found that FMn loss occurred rapidly after axotomy in saline-treated animals and could be best fitted with a decaying exponential relationship (time constant 2.7 days). In the saline-treated animals, the FMn loss plateaued between 7 and 14 days at 74.8%, and 47% of the FMns were found to be lost within 3 days. Increases in the facial nuclear GFAP-OD values and GFAP-AREA values were evident as early as 1 day following axotomy (2.5 and 3.3 times normal, respectively) and reached maximal levels by 7 days (5.7 and 37.6 times normal, respectively). The administration of (-)-deprenyl slowed the loss of the FMns by 24-48 h (time constant 3.9 days) and increased the number of surviving FMns at 21 days by 2.1 times. Treatment with (-)-deprenyl was found to significantly increase GFAP-OD and GFAP-AREA at Day 1 by 71 and 32%, respectively, and at Day 3 by 22 and 27%, respectively. In contrast, it decreased GFAP-OD and GFAP-AREA by 42 and 19%, respectively, at Day 7, and by 20 and 12%, respectively at Day 21. Accordingly, as estimated by both measures, the drug increases reactive astrogliosis in the facial nucleus during the first 3 days after facial nerve transection and decreases the gliosis thereafter.(ABSTRACT TRUNCATED AT 400 WORDS)
(-)-司来吉兰先前已被证明,在出生后第14天(P14)进行轴突切断术导致肌肉源性营养支持丧失后,可增加大鼠面部运动神经元(FMn)的存活率,并在成年大鼠纹状体遭受创伤性损伤后增加反应性星形胶质细胞增生。我们通过两种方法估计了P14时面神经横断后1、3、7、14和21天面部核中的反应性星形胶质细胞增生:第一,通过测量面部核中GFAP免疫反应的相对光密度(OD)(GFAP-OD);第二,通过确定同一核中GFAP免疫反应性的相对面积(GFAP-AREA)。通过使用取自未损伤、年龄匹配动物的相同脑干水平的对照半切片,对每个面部核长度的多个免疫反应切片进行了这两种测量。实验性和对照性面部核半切片采用“粘合”半脑干方法进行共免疫反应。面神经横断用于使同侧面部核中的所有FMn发生轴突切断。在与上述相同的时间点,使用通过每个面部核的连续切片中尼氏染色的胞体计数来检查存活的FMn数量。我们发现,在生理盐水处理的动物中,轴突切断后FMn迅速丧失,并且最适合用衰减指数关系(时间常数2.7天)来拟合。在生理盐水处理的动物中,FMn丧失在7至14天达到平台期,为74.8%,并且发现47%的FMn在3天内丧失。面部核GFAP-OD值和GFAP-AREA值的增加早在轴突切断后1天就很明显(分别为正常的2.5倍和3.3倍),并在7天达到最大值(分别为正常的5.7倍和37.6倍)。(-)-司来吉兰的给药使FMn的丧失延缓24至48小时(时间常数3.9天),并使21天时存活的FMn数量增加2.1倍。发现用(-)-司来吉兰治疗在第1天分别使GFAP-OD和GFAP-AREA显著增加71%和32%,在第3天分别增加22%和27%。相比之下,在第7天它分别使GFAP-OD和GFAP-AREA降低42%和19%,在第21天分别降低20%和12%。因此,通过这两种测量估计,该药物在面神经横断后的前3天增加面部核中的反应性星形胶质细胞增生,此后降低胶质细胞增生。(摘要截短为400字)