Brown J N, Miller J M, Altschuler R A, Nuttall A L
Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-05065.
Hear Res. 1993 Nov;70(2):167-72. doi: 10.1016/0378-5955(93)90155-t.
Continuous long-term delivery of experimental drugs to the cochlea of a small animal, such as a young guinea pig, presents several technical problems. A method of placing and securing a cannula-osmotic pump system is described in this paper. Guinea pigs (225-410 g) were unilaterally implanted with an Alzet micro-pump and cannula for delivery of 20 mM tetrodotoxin (TTX) (six animals) or saline (three animals) for three days (1 microliter/h). Auditory brainstem responses (ABRs) were recorded under light anesthesia on post-implant day 1 and day 3 and compared with pre-implant baseline values. In all six cochleas infused with TTX, most frequencies showed a 30-60dB decrease in sensitivity within 24 h. Saline control animals showed little or no change from baseline sensitivity for most frequencies. In three TTX-infused animals, the cannula-pump unit was removed on day 3, and ABRs were followed during recovery. Most frequencies returned to, or near, pre-implant levels after pump removal but recovery times varied. By day 6, all animals had recovered post-surgical weight loss and showed a gain of 10-40 g. Brains and cochleas were removed and processed for sectioning. Assessment of the cochlear nucleus of non-recovery TTX-treated animals showed a deafness-related flattening of auditory nerve active zones on the treated side.
将实验药物持续长期输送到诸如幼年豚鼠等小动物的耳蜗存在若干技术问题。本文描述了一种放置和固定插管-渗透泵系统的方法。对体重225 - 410克的豚鼠进行单侧植入Alzet微型泵和插管，以每小时1微升的速度输送20毫摩尔的河豚毒素（TTX）（六只动物）或生理盐水（三只动物），持续三天。在植入后的第1天和第3天，在轻度麻醉下记录听觉脑干反应（ABR），并与植入前的基线值进行比较。在所有六只注入TTX的耳蜗中，大多数频率在24小时内灵敏度下降了30 - 60分贝。生理盐水对照动物的大多数频率与基线灵敏度相比几乎没有变化或没有变化。在三只注入TTX的动物中，在第3天移除插管-泵单元，并在恢复过程中跟踪ABR。移除泵后，大多数频率恢复到植入前水平或接近植入前水平，但恢复时间各不相同。到第6天，所有动物术后体重减轻均已恢复，体重增加了10 - 40克。取出大脑和耳蜗并进行切片处理。对未恢复的TTX处理动物的耳蜗核评估显示，处理侧听觉神经活动区出现与耳聋相关的扁平化。
