Neurobiologieal Studies of Experimental Diphenylhydantoin Intoxication–III. Electron Microscopic Studies on Development and Disintegration Mechanism of Altered Axon Terminals and Synaptic Endings in Rat Cerebellum with Chronic Diphenylhydantoin Intoxication

The processes of development and disintegration of axonal spheroids were electron microscopically studied in the rat cerebellum with chronic diphenylhydantoin intoxication. According to the severity and character of membrane accumulation, the whole course ranging from development to disintegration of altered axon terminals and synaptic endings in the DPH-intoxicated rat cerebellum was classified into the following four stages--initial, moderate, advanced and terminal. The initial stage was characterized by the appearance of a small number of interconnected tubules 150 to 350 A in diameter in non-enlarged axon terminals and synaptic endings. Usually these tubular structures tended to congregate in a certain part of axoplasm so that there were no intimate relationships between them and ordinary cell organelles. The moderate stage was characterized by an increased number of interconnected tubules in slightly or moderately swollen axon terminals and synaptic endings. The advanced stage was characterized by an extraordinary number of interconnected tubules in extremely highly swollen axon terminals and synaptic endings. Membranous scrolls and/or membranous strands separated by a cleft-like space were also found in an association with interconnected tubules so that the morphological organization of spheroids in the rat cerebellum with chronic DPH intoxication was very analogous to those of infantile neuroaxonal dystrophy. The terminal stage was characterized by the following three axonal events, i.e., rarefaction and coagulation necroses, and phagocytosis of spheroids by glial elements, presumably astrocytic in origin. The formation and fate of such axonal spheroids have not as yet been shown and discussed by electron microscopists. Thus the present paper was the first to reveal the electron microscopic observations suggestive of the details of development and disintegration mechanisms of spheroids by means of animal experimentations.