Cerebellar morphology: Alterations during graft versus host disease

Impairment of cerebellar development was analyzed at the light microscopic level in 14-day-old F₁ hybrid rats subjected to graft-versus-host disease (GVHD). Grafts of parental strain lymph node cells (PSLNC) were injected into neonatal rats born of Fischer (FI) females mated with Dark Agouti (DA) males. Such grafts resulted in the anemia, body and organ wasting, skin lesions, and death which are characteristic of the syndrome. As we described previously [7], these symptoms occur during the time of postnatal cerebellar development, and abnormal cerebellar development due to experimentally induced GVHD was evident by Day 11, when there was a decrease in DNA synthetic ability. In this report we present results of area and perimeter measurements of the corticla layers of the cerebellum and of cell counting in those layers. There was no change in the overall size of the midsagittal section or the internal granular layer, suggesting that there was no tissue edema. However, the area of the germinal matrix zone, the external granular layer, was markedly decreased and there was a compensatory increase in the size of the underlying molecular layer. This large molecular layer seemed almost devoid of cells and upon counting the cell populations of this layer we found a great reduction in the number of cells migrating from the external to internal granular layer as well as a substantial decrease in the numbers of resident stellate and basket cells. Cell viability may be affected by GVHD since the number of Purkinje cells was also slightly, but significantly, less in diseased animals than in littermate controls. These findings suggest that GVHD is affecting the proliferation, differentiation and migration of external granular layer cells and possibly damaging preexisting cells.