Midazolam administered to 8-day-old mouse pups for three weeks induces cerebellar cortex alterations.

Abstract

Midazolam (MDZ) administered during the neonatal period induces histological changes in the cerebellar cortex of mouse pups. We investigated whether these changes are similar to those induced by prenatal exposure to diazepam (DZ). Two neonatal ICR-strain mouse groups were injected daily from day 8 to 29. The first group (MDZ) was treated with a single daily MDZ dose (2.0 mg/kg/body weight) and the second with saline solution. The mice (10 MDZ and 10 control), were sacrificed in a CO2 atmosphere at 30 days; the cerebellum was fixed in 2.5% glutaraldehyde, post-fixed in 1% OsO4 and embedded in epoxy resin. Semifine sections were stained with toluidine blue and observed under a light microscope. The cerebellar cortex of the MDZ group was thinner than that of controls. The cortex showed a reduced number of Purkinje cells, some with a shrunken cytoplasm and degenerative signs. The dendrite tree was swollen with disoriented branches. Numerous granular cells remained in the molecular layer with few in the granular layer (p<0.05). The nucleus of Purkinje cells and granular cells showed atypical heterochromatin distribution, irregular nuclear surface, and voluminous nucleoli. The neuropile and myelin fibers showed delayed differentiation. Postnatal exposure to MDZ produces similar histological changes in the cerebellar cortex of the 30-day-old mouse treated for 21 days, to those induced by prenatal exposure to DZ.