Elsevier

Neuroscience Letters

Volume 451, Issue 3, 27 February 2009, Pages 232-236
Neuroscience Letters

Factors involved in inflammation-induced developmental white matter damage

https://doi.org/10.1016/j.neulet.2009.01.021Get rights and content

Abstract

Developmental white matter damage is a brain pathology associated with several long-term neurological disorders. An inflammatory insult has been suggested as the major instigating event. This study investigated the relative influence of inflammation, blood–brain barrier permeability and glial ontogeny in white matter damage. Systemic inflammation was induced in Monodelphis domestica (opossum) by serial intraperitoneal injections of lipopolysaccharide at different stages of brain development. Volume of white matter was estimated for the external capsule. Blood–brain barrier permeability was assessed immunocytochemically. Quantitative RT-PCR was used to measure relative levels of mRNA for IL-1β, IL-6 and COX-2. Developmental changes in numbers and appearance of microglia and astrocytes were estimated. Results showed that in response to systemic inflammation, white matter was reduced in the external capsule during a circumscribed period only. At the same developmental stage blood–brain barrier permeability was altered, cerebral inflammatory response was present and numbers of microglia increased. However, the periods of altered blood–brain barrier permeability and the cerebral inflammatory response were longer than the period of the external capsule's susceptibility to white matter damage, which coincided with the developmental increase in the number of astrocytes in this tract. Thus, the mechanism of white matter damage following systemic inflammation is multifactorial, including cerebral inflammation and breakdown of brain barriers occurring simultaneously at specific stages of glial cell development.

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Acknowledgements

This work was supported by a grant from the National Health and Medical Research Council of Australia. The Authors would also like to thank Jessie Truettner from the University of Miami for her help with primer design and validation.

References (21)

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