Non-myelin-forming Schwann cells proliferate rapidly during Wallerian degeneration in the rat sciatic nerve

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Abstract
Summary Transection of a mixed peripheral nerve results in the degeneration of axons and breakdown of myelin in the distal stump. These events are accompanied by a sharp but transient Schwann cell proliferation. The present study seeks to determine whether both myelin-forming and non-myelin-forming Schwann cells enter a proliferative phase under these conditions, or whether the dividing cells are chiefly recruited from one or other of the Schwann cell populations. The macrophage recruitment into the transected distal stumps has also been timed and quantitated, since it has been suggested that macrophages are an important source of Schwann cell mitogens in degenerating peripheral nerves. Incorporation of [3H]-thymidine and autoradiography was used as a measure of cell proliferation, and cell type markers and immunohistochemistry were used to identify myelin-forming and non-myelin-forming Schwann cells. The cells were removed from the distal stump of the rat sciatic nerve and sympathetic trunk at various times after transection and proliferation measured during the first 24 h in culture. It was found that in the sciatic nerve, which contains a mixture of myelinated and unmyelinated fibres, both myelin-forming cells, identified by presence of the myelin protein Po, and non-myelin-forming cells (Po − cells) showed a substantial elevation in [3H]-thymidine labelling index at day 2 postoperatively, which was similar in magnitude for the two categories of cell. The proliferation rate of both Po + and Po − cells remained elevated for up to 8 days after transection. In the largely unmyelinated sympathetic trunk, the peak rate of Po − Schwann cell division reached less than half the peak rate for Po − cells in the sciatic nerve, and cell division fell to a level barely above the control value by postoperative day 4. In the sciatic nerve the number of macrophages, which were identified by monoclonal antibody ED1, rose sharply during the first postoperative day and peaked at day 2. These results provide strong evidence that non-myelin-forming and myelin-forming Schwann cells contribute approximately equally to the initial burst of Schwann cell proliferation seen in the distal stump of the transected rat sciatic nerve. They also indicate that the proliferative response of non-myelin-forming cells is substantially greater in nerves containing many myelinated fibres than in essentially unmyelinated nerves. The timing of macrophage recruitment in the sciatic nerve is consistent with the hypothesis that macrophages are an important source of Schwann cell mitogens during nerve degeneration.