Effect of ischemia on axonal transport of choline acetyltransferase and acetylcholinesterase and on ultrastructural changes of isolated segments of rabbit nerves in situ

Abstract

Axonal transport of acetylcholinesterase (AChE) and choline acetyltransferase (ChAc) and ultrastructural degenerative changes were compared in isolated nerve segments of rabbit peroneal nerves kept in vivo for 22 h, either with preserved blood supply (control segments) or under conditions of ischemia (ischemic segments). Ischemia abolished the proximo-distal and disto-proximal axonal transport of AChE and the proximo-distal transport of ChAc which, in control segments, were revealed by accumulations of the enzymes at corresponding ends of the segments. Total activities of AChE and ChAc recovered in isolated segments with intact blood supply corresponded to the activities in normal nerves; in ischemic segments, 50% of ChAc activity was lost in 22 h, whereas all AChE activity was preserved. Ultrastructural changes were found in few fibres in control segments and in many fibres in ischemic segments 22 h after nerve interruption. The early changes in control segments correspond to those described in the literature for peripheral stump of severed nerves. The microtubules, neurofilaments and mitochondria were not affected. In ischemic segments, various stages of axoplasmic disintegration occurred in the myelinated and unmyelinated axons:flocculation and clumping of axoplasmic material, decomposition of neurofilaments and microtubules, swelling, formation of amorphous densities and breakdown of mitochondrial cristae. Swelling, amorphous densities, clumping of nuclear chromatin and necrotic mitochondrial changes appeared also in Schwann cells. It is concluded that ischemia blocks axonal transport and brings about, within 22 h, ultrastructural changes both in nerve fibres and in Schwann cells. Cytoplasmic ChAc is affected earlier by necrotic degeneration of the axons than membrane-bound AChE.