Ultrastructural changes of the neuromuscular junction in reperfusion injury

Ischemia followed by reperfusion of skeletal muscle frequently takes place in trauma surgery. Anoxia followed by reoxygenation leads to reperfusion injury, which damages the involved tissues. However, no information is available about how the neuromuscular junction is affected by ischemia-reperfusion. Tourniquet ischemia of the left hind limb was applied in the anesthetized rat for 2 h. Reperfusion lasted for 2 and 24 h and for 1, 2 and 4 weeks. The extensor digitorum longus and the soleus muscles from both legs were prepared for electron-microscopic analyses. Morphological changes of the neuromuscular junction were investigated. In all cases only the nerve endings (terminals) were affected. The postsynaptic structures were not affected. Changes can be grouped in two categories: degeneration and recovery. Degeneration consisted of the loss of synaptic vesicles, disruption of the presynaptic membrane, degeneration of the mitochondria and the development of vacuoles. It was most severe at 24 h and was still present at 4 weeks of reperfusion. Recovery started at 1 week of reperfusion and lasted at least for 4 weeks. It consisted of the slow reappearance of synaptic vesicles and mitochondria, and restoration of the presynaptic membrane with active zones. Ultrastructure of the skeletal muscle fibers did not show pathological changes. The recovery of the structures may be regulated by the Schwann cells and also by the postsynaptic membrane which is not affected by 2 h of ischemia followed by reperfusion.