Kaji R, Suzumura A, Sumner A J
Department of Neurology, University of Pennsylvania, Philadelphia.
Brain. 1988 Jun;111 ( Pt 3):675-94. doi: 10.1093/brain/111.3.675.
To study the pathophysiology of immunologically mediated demyelination in the central nervous system (CNS), we injected 20 to 30 microliters of polyclonal antigalactocerebroside serum (AGC) into the lower thoracic dorsal column of the spinal cord in 20 Wistar rats. AGC-injected spinal cords contained areas of fascicular demyelination adjacent to the focus of axonal degeneration at the injection site. Somatosensory evoked potentials were recorded serially after tibial nerve stimulation. In 85% of AGC-injected animals, the following characteristics were observed by 3 days after injection: (1) decreased amplitude of the cortically generated potential (P15); (2) failure of transmission of high-frequency (50 Hz) impulses (rate-dependent block); (3) delayed conduction velocity of the compound action potentials through the lesion. None of these changes was seen in 90% of 20 rats injected with normal saline or control rabbit sera. In 7 rats with acrylamide-induced axonopathy or wallerian degeneration, the rate-dependent block was not observed. The onset of clinical symptoms (hindlimb ataxia) in AGC-injected rats was best correlated with development of the rate-dependent block. Clinical recovery was observed by 14 days after injection concurrent with restoration of P15 amplitude, when the rate-dependent block and decreased conduction velocities were unchanged. High-frequency-resistant conduction was re-established much later than clinical recovery in 3 rats. These findings suggest that failure of high-frequency impulse transmission may produce clinical symptoms and that a central adaptive mechanism to remodulated trains of impulses plays a role in clinical recovery from CNS demyelination.
为研究中枢神经系统（CNS）中免疫介导的脱髓鞘的病理生理学，我们向20只Wistar大鼠脊髓的下胸段背柱注射了20至30微升多克隆抗半乳糖脑苷脂血清（AGC）。注射AGC的脊髓在注射部位轴突变性灶附近存在束状脱髓鞘区域。在刺激胫神经后连续记录体感诱发电位。在85%注射AGC的动物中，注射后3天观察到以下特征：（1）皮质产生电位（P15）的幅度降低；（2）高频（50Hz）冲动传导失败（频率依赖性阻滞）；（3）复合动作电位通过病变部位的传导速度延迟。在注射生理盐水或对照兔血清的20只大鼠中，90%未观察到这些变化。在7只患有丙烯酰胺诱导的轴索性神经病或华勒氏变性的大鼠中，未观察到频率依赖性阻滞。注射AGC的大鼠临床症状（后肢共济失调）的出现与频率依赖性阻滞的发展最相关。注射后14天观察到临床恢复，同时P15幅度恢复，此时频率依赖性阻滞和传导速度降低未改变。在3只大鼠中，高频抗性传导的重建比临床恢复晚得多。这些发现表明，高频冲动传递失败可能产生临床症状，并且一种对冲动序列进行重塑的中枢适应性机制在CNS脱髓鞘的临床恢复中起作用。
