Effect of chronic phenobarbitone toxicity on the cerebellum of adult rats: an electron microscopic study

ABSTRACT

The degenerative effect of chronic phenobarbitone toxicity on the structure of the adult rat cerebellum was studied in this investigation. 24 adult male albino rats were used, 16 of them were daily injected i.m. with 0.02 mg/kg body weight of phenobarbitone for 3 weeks. The remaining rats were injected with sterilized water [control group]. The body weights were recorded before the first injection and after the last one. The animals were killed by intracardiac perfusion of 20 ml of isotonic saline followed by 250 ml of 2.5% gluteraldehyde. The brain of these animals were dissected. The total brain and cerebellar weights were determined. The ratio of cerebellar to brain weight was calculated for each animal. The pyramis vermis of the cerebellum was dissected out and processed for transmission electron microscopy [TEM]. The results revealed that there was a highly significant retardation of body, brain and cerebellar growth of treated animals compared with the control group. There was also a highly significant decrease in the ratio between cerebellar and brain weights of those animals compared with the control group. TEM examination revealed evidence of degeneration in the mitochondria and myelin. Mitochondrial degeneration varied from swelling, fragmentation and disorganization of cristae to complete granulation and, finally, total breakdown of mitochondrial contents. The nuclei are irregular and contain dense chromatin mostly peripheral in position. Myelin degeneration was expressed in scattered regions, where the axonal myelin sheath was made up of dense staining lamellae. Irregularities in membrane wrapping, segmented swelling and disruption of lamellae, uneven staining and spaces within the myelin sheath were manifested such degenerations were found mostly in the granule cell layer