title: Paranodal myelin damage after acute stretch in Guinea pig spinal cord.
abstract: Mechanical injury causes myelin disruption and subsequent axonal conduction failure in the mammalian spinal cord. However, the underlying mechanism is not well understood. In mammalian myelinated axons, proper paranodal myelin structure is crucial for the generation and propagation of action potentials. The exposure of potassium channels at the juxtaparanodal region due to myelin disruption is thought to induce outward potassium currents and inhibit the genesis of the action potential, leading to conduction failure. Using multimodal imaging techniques, we provided anatomical evidence demonstrating paranodal myelin disruption and consequent exposure and redistribution of potassium channels following mechanical insult in the guinea pig spinal cord. Decompaction of paranodal myelin was also observed. It was shown that paranodal demyelination can result from both an initial physical impact and secondary biochemical reactions that are calcium dependent. 4-Aminopyridine (4-AP), a known potassium channel blocker, can partially restore axonal conduction, which further implicates the role of potassium channels in conduction failure. We provide important evidence of paranodal myelin damage, the role of potassium channels in conduction loss, and the therapeutic value of potassium blockade as an effective intervention to restore function following spinal cord trauma.
authors: Department of Basic Medical Sciences, Center for Paralysis Research, Purdue University, West Lafayette, Indiana, USA.
authors: Wenjing
authors: W
authors: Sun
authors: Yan
authors: Y
authors: Fu
authors: Yuzhou
authors: Y
authors: Shi
authors: Ji-Xin
authors: JX
authors: Cheng
authors: Peng
authors: P
authors: Cao
authors: Riyi
authors: R
authors: Shi
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001711:Biotransformation / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002154:Calpain / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D008853:Microscopy; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000473:pathology*; D009431:Neural Conduction / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology*
chemical_list: D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009553:Nimodipine; D015761:4-Aminopyridine; D002154:Calpain; D002118:Calcium