Tong J X, Rich K M
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Neurocytol. 1997 May;26(5):339-47. doi: 10.1023/a:1018508819191.
Immature rat facial motoneurons are very sensitive to injury with nearly 80% dying during the first week after axotomy. This motoneuron death is apoptotic, similar to that induced in neurons after tropic factor withdrawal. The diphenylpiperazines, flunarizine and cinnarizine, protect dorsal root ganglion neurons from death after withdrawal of trophic support, i.e., nerve growth factor withdrawal, in vitro. Similarly, the monoamine oxidase inhibitor, deprenyl, promotes survival of facial motoneurons after axotomy. These pharmacological agents were assessed both alone and in combination for their ability to prevent death in non-nerve growth factor dependent CNS motoneurons after facial nerve axotomy in newborn rats. Long-term experiments were done with the diphenylpiperazines to evaluate potential enhancement of regeneration. Facial nerve transection resulted in 78% neuronal loss in the injured compared with the contralateral, uninjured nucleus. Systemic administration of diphenylpiperazines for 1 week after facial nerve transection doubled the number of surviving motoneurons from 23% to 47%. Similar results were obtained with deprenyl. Combinations of diphenylpiperazines and deprenyl provide a similar degree of neuronal protection 1 week after injury as that obtained by either agent alone. We assessed the ability of diphenylpiperazines to protect facial motoneurons from death over a prolonged period and enhance subsequent regeneration. Motor neuron counts in rats treated with diphenylpiperazines for 1 month after injury and assessed 2 months later demonstrated long-term enhancement of neuronal protection with an increase of 45% in the number of horseradish peroxidase-labelled motoneurons. The diphenylpiperazines group had approximately 80% more regenerated myelinated axons in the distal facial nerve than the control group. Thus, diphenylpiperazine treatment during the first month after injury provides long-term protection of non-nerve growth factor dependent CNS motoneurons with subsequent potentiation of long-term facial nerve regeneration.
未成熟大鼠的面神经运动神经元对损伤非常敏感，在轴突切断后的第一周内，近80%的神经元会死亡。这种运动神经元死亡是凋亡性的，类似于在神经营养因子撤除后神经元中诱导的死亡。二苯基哌嗪类药物氟桂利嗪和桂利嗪，在体外可保护背根神经节神经元在营养支持撤除后，即神经生长因子撤除后免于死亡。同样，单胺氧化酶抑制剂司来吉兰可促进面神经切断后面神经运动神经元的存活。对这些药物单独及联合使用预防新生大鼠面神经切断后非神经生长因子依赖性中枢神经系统运动神经元死亡的能力进行了评估。对二苯基哌嗪类药物进行了长期实验，以评估其对再生的潜在促进作用。与对侧未损伤的核相比，面神经横断导致损伤侧78%的神经元丢失。面神经横断后全身给予二苯基哌嗪类药物1周，使存活运动神经元的数量从23%增加到47%，增加了一倍。司来吉兰也得到了类似的结果。二苯基哌嗪类药物和司来吉兰联合使用在损伤后1周提供的神经元保护程度与单独使用任何一种药物相似。我们评估了二苯基哌嗪类药物在较长时间内保护面神经运动神经元免于死亡并增强随后再生的能力。损伤后用二苯基哌嗪类药物治疗1个月并在2个月后评估的大鼠运动神经元计数显示，神经元保护作用长期增强，辣根过氧化物酶标记的运动神经元数量增加了45%。与对照组相比，二苯基哌嗪类药物组远端面神经中再生的有髓轴突多约80%。因此，损伤后第一个月进行二苯基哌嗪治疗可长期保护非神经生长因子依赖性中枢神经系统运动神经元，并随后增强面神经的长期再生。
