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A型肉毒杆菌神经毒素的剂量依赖性中枢效应:对清醒行为猫的初步研究

Dose-dependent, central effects of botulinum neurotoxin type A: a pilot study in the alert behaving cat.

作者信息

Moreno-López B, Pastor A M, de la Cruz R R, Delgado-García J M

机构信息

Laboratorio de Neurociencia, Facultad de Biología, Universidad de Sevilla, Spain.

出版信息

Neurology. 1997 Feb;48(2):456-64. doi: 10.1212/wnl.48.2.456.

DOI:10.1212/wnl.48.2.456
PMID:9040739
Abstract

We investigated, in alert behaving cats, the long-term effects of botulinum neurotoxin (BoNT) type A injected into the lateral rectus muscle of the eye. We studied orthodromic field potentials recorded in the injected muscle, eye movements, and the discharge characteristics of the innervating abducens motoneurons. Single BoNT injections at doses from 0.01 to 0.3 ng/kg reduced, or even completely eliminated, eye movements in the abducting direction for up to 2 months without affecting the motoneuron discharge profile that remained related to actual eye movements of the contralateral unparalyzed eye. This result indicates that abducens motoneurons were still under the influence of the ocular motor central control system regardless of their ineffective action on lateral rectus muscle fibers. We also conclude that paralysis per se is not enough to initiate axotomy-like neural responses in ocular motoneurons. The injection of BoNT at a dose of 3 ng/kg produced significant changes in the discharge pattern of abducens motoneurons lasting up to 3 months-the maximum time checked. This finding was probably due to retrograde and, perhaps, transneuronal effects of BoNT when injected in a high dose. The results give some indications of the maximum allowable dose that can be used without the induction of unwanted side effects in the motoneuronal pool innervating the injected muscle.

摘要

我们在清醒状态下的猫身上,研究了向眼外直肌注射A型肉毒杆菌神经毒素(BoNT)的长期影响。我们研究了在注射肌肉中记录的顺向场电位、眼球运动以及支配展神经运动神经元的放电特性。以0.01至0.3 ng/kg的剂量单次注射BoNT,可减少甚至完全消除外展方向的眼球运动,持续长达2个月,而不影响运动神经元的放电模式,该模式仍与对侧未麻痹眼睛的实际眼球运动相关。这一结果表明,展神经运动神经元仍受眼动中枢控制系统的影响,尽管它们对外直肌纤维的作用无效。我们还得出结论,麻痹本身不足以引发眼运动神经元中类似轴突切断的神经反应。以3 ng/kg的剂量注射BoNT,会使展神经运动神经元的放电模式产生显著变化,持续长达3个月——这是检查的最长时间。这一发现可能是由于高剂量注射BoNT时的逆行作用,或许还有跨神经元作用。这些结果为在不诱导支配注射肌肉的运动神经元池产生不良副作用的情况下可使用的最大允许剂量提供了一些指示。

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