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Stereological Analysis of Regional Brain Volumes and Neuron Numbers in Rats Displaying a Spontaneous Hydrocephalic Condition

Stereological methods were employed to investigate a novel spontaneously occurring brain mutation in an inbred colony of Wistar rats. These mutants displayed changes (enlarged cerebral ventricles and malformed hippocampi) similar to those seen in H-Tx hydrocephalic rats. Mutant and control rats were studied at three postnatal ages: 4, 7, and 13 weeks. Brain weight in the mutant animals was significantly (P < 0.05) increased when compared to age-matched controls. Using systematic random sampling and the Cavalieri principle we estimated the volumes of various brain compartments, including the cerebral ventricles, forebrain, and cerebral cortex. We found that ventricular volume (P < 0.001) and forebrain volume (P < 0.05) were significantly increased in mutant rats when compared to control rats. Total numbers of nucleoli, estimated using the physical fractionator, were obtained for neurons in the cerebral cortex and granule cells in the dentate gyrus. Numbers were not altered significantly in mutant rats. Nor were mean soma volumes as estimated from total volumes and numbers. The changes in brain and ventricle volumes provide quantitative evidence that these animals display a hydrocephalic condition. This condition appears not to compromise cell number or mean soma size in the brain regions examined.