Do early lesions affect cell death in the central nervous system? A study on the effects of early cerebellar hemispherectomy in rats

Abstract

Cell death patterns in the lateral and interposed nuclei were compared in control rats and rats in whom a unilateral cerebellar hemispherectomy was performed at day 2 of life. Both groups were studied between days 2 and 20 of life. Pyknotic cells and live neuronal and glial cells were counted from Nissl stained sections. After correction of these values, pyknotic to live cell ratios were calculated. In the lateral nucleus of normal rats, around 14-28 pyknotic cells per 1,000 live cells occurred from day 2 to day 12. Thereafter this value decreased, and from day 16 less than 3 pyknotic/1,000 live cells were observed. In the interposed nuclei, 18-28 pyknotic cells/1,000 live cells occurred at day 2, and from this age onward values gradually decreased. At day 20 values ranged around 1.6/1,000. After unilateral cerebellar hemispherectomy, values in both nuclei began to decrease as early as from day 8. Results from the present study strongly suggest that these cells are prevented from dying because they find an aberrant synaptic target in the ipsilateral red nucleus. Our results demonstrate that early lesions interfere with the regulation of fundamental processes of neuro-ontogeny.

Normal and Abnormal Development of Motor Behavior:Lessons From Experiments in Rats

“…One of the most plausible possibilities seemed that the aberrantly projecting neurons emanate from supernumerary neurons in the deep cerebellar nuclei; neurones which normally die during early development. This possibility was investigated by inventarising cell death patterns in the deep cerebellar nuclei from P2 until P20 (Gramsbergen & IJkema-Paassen, 1987). In normal rats, neuronal cell death in the cerebellar nuclei stops at about the 15 tn day, but after a cerebellar hemispherectomy at P2, this process ends already at P8.…”