Department of Neurology, Brain Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Biomedical Signals and Systems, MIRA, Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
J Neurophysiol. 2019 Sep 1;122(3):1036-1049. doi: 10.1152/jn.00326.2019. Epub 2019 Jul 10.
Immune-mediated neuropathies affect myelinated axons, resulting in conduction slowing or block that may affect motor and sensory axons differently. The underlying mechanisms of these neuropathies are not well understood. Using a myelinated axon model, we studied the impact of perinodal changes on conduction. We extended a longitudinal axon model (41 nodes of Ranvier) with biophysical properties unique to human myelinated motor and sensory axons. We simulated effects of temperature and axonal diameter on conduction and strength-duration properties. We then studied effects of impaired nodal sodium channel conductance and paranodal myelin detachment by reducing periaxonal resistance, as well as their interaction, on conduction in the 9 middle nodes and enclosed paranodes. Finally, we assessed the impact of reducing the affected region (5 nodes) and adding nodal widening. Physiological motor and sensory conduction velocities and changes to axonal diameter and temperature were observed. The sensory axon had a longer strength-duration time constant. Reducing sodium channel conductance and paranodal periaxonal resistance induced progressive conduction slowing. In motor axons, conduction block occurred with a 4-fold drop in sodium channel conductance or a 7.7-fold drop in periaxonal resistance. In sensory axons, block arose with a 4.8-fold drop in sodium channel conductance or a 9-fold drop in periaxonal resistance. This indicated that motor axons are more vulnerable to developing block. A boundary of block emerged when the two mechanisms interacted. This boundary shifted in opposite directions for a smaller affected region and nodal widening. These differences may contribute to the predominance of motor deficits observed in some immune-mediated neuropathies. Immune-mediated neuropathies may affect myelinated motor and sensory axons differently. By the development of a computational model, we quantitatively studied the impact of perinodal changes on conduction in motor and sensory axons. Simulations of increasing nodal sodium channel dysfunction and paranodal myelin detachment induced progressive conduction slowing. Sensory axons were more resistant to block than motor axons. This could explain the greater predisposition of motor axons to functional deficits observed in some immune-mediated neuropathies.
免疫介导性神经病影响有髓轴突，导致传导减慢或阻滞，可能对运动和感觉轴突产生不同的影响。这些神经病的潜在机制尚不清楚。我们使用有髓轴突模型研究了连接点变化对传导的影响。我们扩展了一个纵向轴突模型（41 个郎飞结），其中包含人类有髓运动和感觉轴突特有的生物物理特性。我们模拟了温度和轴突直径对传导和强度-时间特性的影响。然后，我们研究了减少轴周电阻对连接点钠通道电导和连接点髓鞘脱离的影响，以及它们对 9 个中间连接点和封闭连接点区域传导的相互作用。最后，我们评估了减少受影响区域（5 个连接点）和增加连接点增宽对传导的影响。观察到生理运动和感觉传导速度以及轴突直径和温度的变化。感觉轴突的强度-时间常数较长。减少钠通道电导和连接点轴周电阻会导致传导逐渐减慢。在运动轴突中，当钠通道电导降低 4 倍或轴周电阻降低 7.7 倍时，会发生传导阻滞。在感觉轴突中，当钠通道电导降低 4.8 倍或轴周电阻降低 9 倍时，会发生传导阻滞。这表明运动轴突更容易发生阻滞。当两种机制相互作用时，阻滞的边界就会出现。当两种机制相互作用时，这个边界会向相反的方向移动，受影响的区域变小，连接点增宽。这些差异可能导致一些免疫介导性神经病中观察到的运动功能缺陷更为突出。免疫介导性神经病可能对有髓运动和感觉轴突产生不同的影响。通过建立计算模型，我们定量研究了连接点变化对运动和感觉轴突传导的影响。模拟增加连接点钠通道功能障碍和连接点髓鞘脱离会导致传导逐渐减慢。感觉轴突比运动轴突更能抵抗阻滞。这可以解释为什么在一些免疫介导性神经病中，运动轴突更容易出现功能缺陷。
