In the monograph of Santiago Ramon y Cajal, he provided a detailed description about the morphological changes in degeneration and regeneration of peripheral and central nervous systems following lesions. He discussed factors that may promote or inhibit axonal growth after peripheral and/or central nerve injury. Cajal with a brilliant insight anticipated the existence of several factors acting on degeneration and regeneration. Free radicals have been proposed to be one of such factors. These highly reactive oxygen species-derived free radicals play a pathogenetic role in neurological disorders, including ischemia, trauma, Alzheimer's disease and Parkinson's disease (PD). In this review we will discuss the similarities and differences between the morphological changes under oxidant stress and Cajal's drawings of degeneration and regeneration following the central injury. The monoaminergic neuron systems in the brainstem appear vulnerable to these free radicals, which have also been implicated in the selective degeneration of the nigrostriatal DA system. We analyzed the degeneration of fibers and the neuronal cell death of brainstem monoaminergic neuron systems in a mutant rat, which has abnormal metabolism of oxygen species in the brain. The degeneration of DA cell bodies and fibers was characterized by swollen varicosities and clustered fibers.
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