Graft-versus-host disease impairs cerebellar growth

Abstract

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.