Department of Basic Medical Sciences, School of Veterinary Medicine, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA.
Neurosci Bull. 2011 Feb;27(1):36-44. doi: 10.1007/s12264-011-1048-y.
Most axons in the vertebral central nervous system are myelinated by oligodendrocytes. Myelin protects and insulates neuronal processes, enabling the fast, saltatory conduction unique to myelinated axons. Myelin disruption resulting from trauma and biochemical reaction is a common pathological event in spinal cord injury and chronic neurodegenerative diseases. Myelin damage-induced axonal conduction block is considered to be a significant contributor to the devastating neurological deficits resulting from trauma and illness. Potassium channels are believed to play an important role in axonal conduction failure in spinal cord injury and multiple sclerosis. Myelin damage has been shown to unmask potassium channels, creating aberrant potassium currents that inhibit conduction. Potassium channel blockade reduces this ionic leakage and improves conduction. The present review was mainly focused on the development of this technique of restoring axonal conduction and neurological function of demyelinated axons. The drug 4-aminopyridine has recently shown clinical success in treating multiple sclerosis symptoms. Further translational research has also identified several novel potassium channel blockers that may prove effective in restoring axonal conduction.
脊椎中枢神经系统中的大多数轴突是由少突胶质细胞髓鞘形成的。髓鞘保护和隔离神经元的突起,使髓鞘化轴突具有独特的快速跳跃式传导。创伤和生化反应导致的髓鞘破坏是脊髓损伤和慢性神经退行性疾病的常见病理事件。髓鞘损伤诱导的轴突传导阻滞被认为是创伤和疾病导致毁灭性神经功能缺损的重要原因。钾通道被认为在脊髓损伤和多发性硬化症中轴突传导失败中发挥重要作用。髓鞘损伤已被证明能揭示钾通道,产生异常的钾电流,抑制传导。钾通道阻断可减少这种离子渗漏,改善传导。本综述主要集中在恢复脱髓鞘轴突的轴突传导和神经功能的这一技术的发展上。最近,药物 4-氨基吡啶在治疗多发性硬化症症状方面取得了临床成功。进一步的转化研究还确定了几种新型钾通道阻断剂,它们可能在恢复轴突传导方面有效。