Distinctive functional deficiencies in axonal conduction associated with two forms of cerebral white matter injury

This study determines whether assessment with compound action potentials (CAPs) can distinguish two different forms of cerebral white matter injury at the functional levels.

A pure demyelination model was induced in C57/BL6 adult mice by dietary supplementation of cuprizone (0.2%) for 6 weeks. Callosal L-N5-(1-Iminoethyl) ornithine (L-NIO) hydrochloride (27 mg/mL) was injected into the corpus callosum (CC) to induce a focal white matter stroke (WMS), resulting in both demyelination and axonal injury. White matter integrity was assessed by performing CAP recording, electron microscopy, and immunohistological and luxol fast blue (LFB) staining.

Immunohistological and electron microscopic analyses confirmed the induction of robust demyelination in CC with cuprizone, and mixed demyelination and axonal damage with L-NIO. Electrophysiologically, cuprizone-induced demyelination significantly reduced the amplitude of negative peak 1 (N1), but increased the amplitude of negative peak 2 (N2), of the CAPs compared to the sham controls. However, cuprizone did not affect the axonal conduction velocity. In contrast, the amplitude and area of both N1 and N2 along with N1 axonal conduction velocity were dramatically decreased in L-NIO-induced WMS.

Concertedly, parameters of the CAPs offer a novel functional assessment strategy for cerebral white matter injury in rodent models.