Abstract
Extract: Human infants with cytomegalovirus and herpes simplex are presently treated with floxuridine (5-FUDR), a DNA synthesis blocking agent. Since in the cerebellum of the newborn infant neuron formation continues for some time after birth, the question arises whether 5-FUDR might cause permanent damage to the cerebellum. In our experiment 21 2-day-old mice were treated by three injections of 5-FUDR (50 mg/kg body weight per injection), and particular attention was given to damage and subsequent repair of the external granular layer, the site of postnatal neuron formation. In the anterior lobes of the vermis most proliferating external granular cells died and repair was minimal. Purkinje cells were dispersed and few if any basket cells were formed. In the posterior lobes, including the uvula, considerable repair of the external granular layer was noted. The final cerebellar architecture, however, was never normal, and heterotopic granule cell nests were found in the molecular layer. In the intermediary lobes repair occurred, but Purkinje cells were found throughout the granular layer. Since the human cerebellum at birth is characterized by a thick external granular layer, it is not impossible that 5-FUDR may also cause disturbances in the human cerebellar architecture and function.
Speculation: In the cerebellum of the newborn mouse and newborn infant important neurons are formed after birth. Therapy with drugs interfering with DNA, RNA, or protein synthesis should therefore be avoided. Although repair may occur in the gastrointestinal tract, experiments with mice suggest that repair of damage in the cerebellum is minimal. Whether ectopic cell nests in the molecular layer will start cell proliferation during further life is presently not known.
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Langman, J., Shimada, M. & Rodier, P. Floxuridine and Its Influence on Postnatal Cerebellar Development. Pediatr Res 6, 758–764 (1972). https://doi.org/10.1203/00006450-197210000-00003
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DOI: https://doi.org/10.1203/00006450-197210000-00003