Ultrastructural alterations of perineurial cells in the early stage of Wallerian degeneration.

Ultrastructural changes of the perineurium in the distal segment of the mouse phrenic nerve after crush were studied at various intervals of up to 56 days. In the control, the perineurium of the phrenic nerves was composed of multilayered perineurial cells joined together by tight junctions forming concentric laminae surrounding the endoneurium which mainly contained myelinated fibers with a relatively small amount of unmyelinated fibers. In the experiment, perineurial cells showed prominent morphological changes from day 3 to day 6 with the presence of proteinaceous exudate between the cellular laminae of the perineurium. Some of the perineurial cells appeared hypertrophic and often showed mitotic figures. Newly formed gaps between the perineurial cells forming the same lamina as well as between those of adjacent laminae were frequently observed. Intracellular microcavities in the perineurial cells associated with increased pinocytotic vesicles were also observed. In addition, debris-free macrophages were occasionally seen in the perineurium. At this stage, axonal degeneration, myelin breakdown and interstitial proteinaceous exudate, which were already noticed on day 2, were evident in the endoneurium, demonstrating the early stage of Wallerian degeneration. From day 7 on, however, mitotic figures of perineurial cells were not encountered. Perineurial cells of inner laminae contained lipid droplets which increased in number with time. Our observations strongly suggest that perineurial cells play an important role in the early stage of Wallerian degeneration of the peripheral nerve.