Cerebrospinal Fluid Research

During inflammatory conditions of the central nervous system (CNS), such as in multiple sclerosis or in its animal model, experimental autoimmune encephalomyelitis (EAE), immune cells migrate from the blood stream into the CNS parenchyma and into the cerebrospinal fluid (CSF) spaces. The endothelial blood-brain barrier (BBB) has been considered the most obvious entry site for circulating immune cells. Recently, the choroid plexus has been considered as an alternative entry site for circulating lymphocytes into the CSF. The choroid plexus, belongs to the circumventricular organs (CVOs) localized in the walls of the ventricles. Other CVOs, which similar to the choroid plexus lack an endothelial BBB, have not been considered as possible entry sites for immune cells into the CNS parenchyma or the CSF. Here we asked, whether CVOs are involved in the recruitment of inflammatory cells into the brain during EAE. We performed an extensive immunohistological study on the area postrema (AP), the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT) and the median eminence (ME) in frozen brain sections from healthy SJL mice and mice suffering from EAE. Expression of cell adhesion molecules, the presence of leukocyte subpopulations and the detection of major histocompatibility complex antigen expression was compared. Similar changes were observed for all four CVOs included in this study. During EAE significantly increased numbers of CD45+ leukocytes were detected within the four CVOs investigated, the majority of which stained positive for the macrophage markers F4/80 and Mac-1. The adhesion molecules ICAM-1 and VCAM-1 were upregulated on the fenestrated capillaries within the CVOs. A considerable upregulation of MHC class I throughout the CVOs and positive immunostaining for MHC class II on perivascular cells additionally documented the immune activation of the CVOs during EAE. A significant enrichment of inflammatory infiltrates was observed in close vicinity to the CVOs. Our data indicate that the CVOs are a site for the entry of immune cells into the CNS and CSF and consequently are involved in the inflammatory process in the CNS during EAE.

From 1963 to 1971, 117 babies with open spina bifida were treated non-selectively from birth. In 2002 we reviewed all the survivors by postal questionnaire and telephone call. The aims were to find out how many were living independently in the community or were in open employment or drove a car. In addition to these achievements we recorded health, medication and admissions to hospital and asked how much daily help they needed. Ascertainment was 100%. There had been 63 deaths, mainly of the most severely affected. The mean age of the 54 survivors was 35 years. The outcome in terms of disability ranged from apparent normality to total dependency. It reflected both the neurological deficit, which had been recorded in infancy in terms of sensory level, and events in the CSF shunt history. Overall about 2 in 5 of the survivors lived independently in the community, 2 in 5 drove a car, 1 in 5 was in competitive employment and 1 in 5 could walk 50 metres. Although those who survived to age 35 years tended to be less disabled, 2 in 5 continued to need daily care.