Emmett C J, Aswani S P, Stewart G R, Fairchild D, Johnson R M
Department of Neurosciences, Syntex Discovery Research, Palo Alto, CA 94303, USA.
Brain Res. 1995 Mar 6;673(2):199-207. doi: 10.1016/0006-8993(94)01414-d.
Both nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) have been proposed for the treatment of Alzheimer's disease. This study describes a comparative, dose-response analysis of recombinant human (rh)NGF and rhbFGF in a rat unilateral fimbria-fornix model of acute cholinergic neuronal degeneration. Doses for rhNGF were 0.6, 6, 60, 600 and 1,800 ng/rat/day and for rhbFGF were 600, 1,800, 3,000 and 6,000 ng/rat/day, delivered for 4 weeks. The number of surviving septal cholinergic neurons was evaluated using ChAT immunohistochemistry. In control animals, the number of ChAT-positive neurons remaining on the lesioned side was between 22 and 18% compared to the non-lesioned side. Infusion with either neurotrophic factor increased the number of ChAT-positive neurons on the lesioned side in a dose-dependent manner. The maximal response to rhbFGF peaked at 3,000 ng/rat/day with a cell savings of 47%. However, there was evidence of neuropathological changes associated with rhbFGF. In contrast, rhNGF produced a maximal response with an infusion of 600 ng rhNGF/rat/day and a cell savings of 70% and no evidence of neuropathology, indicating that rhNGF was better tolerated and more efficacious than rhbFGF.
神经生长因子（NGF）和碱性成纤维细胞生长因子（bFGF）都已被提议用于治疗阿尔茨海默病。本研究描述了在大鼠单侧穹窿 - 海马伞急性胆碱能神经元变性模型中，重组人（rh）NGF和rhbFGF的比较性剂量反应分析。rhNGF的剂量为0.6、6、60、600和1800 ng/大鼠/天，rhbFGF的剂量为600、1800、3000和6000 ng/大鼠/天，给药4周。使用ChAT免疫组织化学评估存活的隔区胆碱能神经元数量。在对照动物中，与未损伤侧相比，损伤侧剩余的ChAT阳性神经元数量在22%至18%之间。注入任何一种神经营养因子都会使损伤侧ChAT阳性神经元数量呈剂量依赖性增加。rhbFGF的最大反应在3000 ng/大鼠/天时达到峰值，细胞挽救率为47%。然而，有证据表明与rhbFGF相关的神经病理变化。相比之下，rhNGF在注入600 ng rhNGF/大鼠/天时产生最大反应，细胞挽救率为70%，且没有神经病理学证据，表明rhNGF比rhbFGF耐受性更好且更有效。
