Emmett C J, Stewart G R, Johnson R M, Aswani S P, Chan R L, Jakeman L B
Department of Neurobiology, Roche Bioscience, Palo Alto, California 94303, USA.
Exp Neurol. 1996 Aug;140(2):151-60. doi: 10.1006/exnr.1996.0125.
The distribution of radioiodinated recombinant human nerve growth factor ([125I]rhNGF) was evaluated in adult cynomolgus monkeys following unilateral intracerebroventricular (icv) administration. Animals were cannulated into the right ventricle and recovered for 7 days. Monkeys were infused with 1.2 micrograms of [125I]rhNGF or [125I]rhNGF with a 140-fold excess of rhNGF. Twenty-four hours after infusion, animals were anesthetized and transcardially perfused with an aldehyde fixative. Coronal brain sections were processed for quantitative film autoradiography or for choline-acetyltransferase immunohistochemistry and then emulsion dipped. Specific radiolabel was distributed bilaterally and, with equal density, throughout the basal forebrain and was colocalized with choline acetyltransferase-positive neurons. Specific labeling was also present in the superficial ventral cortex. Nonspecific binding was observed surrounding the ventricles and lining blood vessels. These results demonstrate that unilateral icv infusion is an effective approach for delivering NGF to basal forebrain cholinergic neurons in primates and represents a viable drug delivery strategy for the therapeutic use of NGF in Alzheimer's Disease.
在成年食蟹猴单侧脑室内（icv）给药后，评估了放射性碘化重组人神经生长因子（[125I]rhNGF）的分布情况。将动物插管至右心室并恢复7天。给猴子输注1.2微克[125I]rhNGF或加入140倍过量rhNGF的[125I]rhNGF。输注后24小时，将动物麻醉并经心脏用醛类固定剂灌注。对冠状脑切片进行定量胶片放射自显影或胆碱乙酰转移酶免疫组织化学处理，然后进行乳胶浸渍。特异性放射性标记物双侧分布，密度相等，遍布整个基底前脑，并与胆碱乙酰转移酶阳性神经元共定位。在腹侧浅皮层也有特异性标记。在脑室周围和血管内壁观察到非特异性结合。这些结果表明，单侧icv输注是将NGF递送至灵长类动物基底前脑胆碱能神经元的有效方法，并且代表了在阿尔茨海默病中治疗性使用NGF的可行药物递送策略。
