%0 Journal Article
%T Effects of Neonatal Systemic Inflammation on Blood-Brain Barrier Permeability and Behaviour in Juvenile and Adult Rats
%A H. B. Stolp
%A P. A. Johansson
%A M. D. Habgood
%A K. M. Dziegielewska
%A N. R. Saunders
%A C. J. Ek
%J Cardiovascular Psychiatry and Neurology
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/469046
%X Several neurological disorders have been linked to inflammatory insults suffered during development. We investigated the effects of neonatal systemic inflammation, induced by LPS injections, on blood-brain barrier permeability, endothelial tight junctions and behaviour of juvenile (P20) and adult rats. LPS-treatment resulted in altered cellular localisation of claudin-5 and changes in ultrastructural morphology of a few cerebral blood vessels. Barrier permeability to sucrose was significantly increased in LPS treated animals when adult but not at P20 or earlier. Behavioural tests showed that LPS treated animals at P20 exhibited altered behaviour using prepulse inhibition (PPI) analysis, whereas adults demonstrated altered behaviour in the dark/light test. These data indicate that an inflammatory insult during brain development can change blood-brain barrier permeability and behaviour in later life. It also suggests that the impact of inflammation can occur in several phases (short- and long-term) and that each phase might lead to different behavioural modifications. 1. Introduction Human data related to disorders such as autism, schizophrenia, and cerebral palsy indicate that a period of infection/inflammation during specific stages of brain development may act as a triggering insult [1¨C4]. In animal experimental studies, inflammation induced during the early postnatal period in rodents has been associated with increased blood-brain barrier permeability [5], white matter damage [6¨C13], ventricular enlargement [9, 14], and reduced neuron numbers in regions of the hippocampus and cerebellum [15, 16]. In addition, in animals exposed to inflammation in utero or during early postnatal life, long-term behavioural alterations such as deficits in prepulse inhibition test [17, 18], motor behaviour [19], and learning and memory [19, 20] have also been reported. However, the biological mechanisms involved in these pathologies are still not understood. To date there are no studies that directly investigated possible links between changes in blood-brain barrier permeability and behavioural alterations in animals exposed to an inflammatory mediator during early stages of brain development. In this study, we have investigated possible correlations between some behavioural tests and blood-brain barrier morphology and permeability in adolescent and adult rats that were exposed to a prolonged inflammatory stimulus (LPS-injections) as neonates. To examine possible cellular mechanisms behind the alteration in blood-brain barrier permeability, the distribution of claudin-5,
%U http://www.hindawi.com/journals/cpn/2011/469046/