Liberini P, Pioro E P, Maysinger D, Ervin F R, Cuello A C
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Neuroscience. 1993 Apr;53(3):625-37. doi: 10.1016/0306-4522(93)90611-i.
Neocortical infarction induces biochemical and morphological retrograde degenerative changes in cholinergic neurons of the rat nucleus basalis magnocellularis [Sofroniew et al. (1983) Brain Res. 289, 370-374]. In the present study, this lesion model has been reproduced in the non-human primate (Cercopithecus aethiops) to investigate whether degenerative changes affecting the cortex surrounding the lesioned area and the ipsilateral basal forebrain are prevented by the early administration of recombinant human nerve growth factor alone or in combination with the monosialoganglioside GM1. Six months after surgery and treatment, the monkeys were processed either for biochemistry (choline acetyltransferase assay) or immunocytochemistry. In lesioned vehicle-treated animals, choline acetyltransferase activity significantly decreased by 28% in the cortex surrounding the injured area and by 31% in the ipsilateral nucleus basalis of Meynert when compared with values of sham-operated monkeys. These biochemical changes were fully prevented with the administration of nerve growth factor alone or in combination with the monosialoganglioside GM1. The morphometrical analysis revealed a significant shrinkage of cholinergic neurons (61 +/- 1.4% of sham-operated cell size) and loss of neuritic processes (59 +/- 10% of sham-operated values) within the intermediate nucleus basalis region of lesioned vehicle-treated animals. Although a protection of the cholinergic cell bodies within the nucleus basalis was found with both treatments, a significant recovery of the neuritic processes (84 +/- 7.2% of sham-operated values) was assessed only in the double-treated monkeys. These results indicate that the early administration of nerve growth factor alone or in combination with the monosialoganglioside GM1 induces a long-term protective effect on the nucleus basalis cholinergic neurons in cortical injured non-human primates.
新皮质梗死可诱导大鼠大细胞基底核胆碱能神经元发生生化和形态学逆行性退行性变化[索夫罗尼耶夫等人（1983年），《脑研究》289卷，370 - 374页]。在本研究中，已在非人灵长类动物（埃塞俄比亚猕猴）中复制了这种损伤模型，以研究单独早期给予重组人神经生长因子或与单唾液酸神经节苷脂GM1联合使用是否能预防影响损伤区域周围皮质和同侧基底前脑的退行性变化。手术和治疗6个月后，对猴子进行生化分析（胆碱乙酰转移酶测定）或免疫细胞化学处理。与假手术猴子的值相比，在损伤后接受载体治疗的动物中，损伤区域周围皮质的胆碱乙酰转移酶活性显著降低28%，同侧迈内特基底核降低31%。单独给予神经生长因子或与单唾液酸神经节苷脂GM1联合使用可完全预防这些生化变化。形态计量分析显示，在损伤后接受载体治疗的动物的基底核中间区域，胆碱能神经元显著萎缩（为假手术细胞大小的61±1.4%），神经突起丢失（为假手术值的59±10%）。虽然两种治疗方法都发现对基底核内的胆碱能细胞体有保护作用，但仅在接受双重治疗的猴子中评估到神经突起有显著恢复（为假手术值的84±7.2%）。这些结果表明，单独早期给予神经生长因子或与单唾液酸神经节苷脂GM1联合使用，可对皮质损伤的非人灵长类动物的基底核胆碱能神经元产生长期保护作用。
