Graft-versus-host disease impairs cerebellar growth [15]

THE mechanisms of mental retardation are of critical interest to both basic developmental neurobiologists and those in the clinical community concerned with perinatal development. The possibility of a deleterious immunological interaction between mother and fetus has long been recognised as a potential developmental hazard¹. However, there have been no reports of specific conditions which involve immunological injury to the developing brain. Graft-versus-host disease (GVHD) is a model disease that can be induced naturally or experimentally by grafting mature, immunocompetent lymphoid cells into an immature, immunoincompetent host. The failure of the host, for example a newborn rat pup, to recognise the graft as non-self leads to an attack by the grafted cells on host lymphomyeloid tissues, resulting in many symptoms, including wasting, anaemia, alterations of lymphoid organ weights, hyperex-citability and an ataxic-like gait². The last two features suggest possible brain dysfunctions and have motivated our investigation of immunologically induced perinatal brain injury. The rat cerebellum was used here as a model system for the study of brain alterations during GVHD because of its well known cytoarchitecture³. In addition, its postnatal development renders it sensitive to many forms of perinatal stress^4,5. In this study, we demonstrate that significant alterations in the cerebellar cellular content and capacity for DNA synthesis occur in rats suffering from neonatally induced GVHD.