Stolp Helen B, Ek C Joakim, Johansson Pia A, Dziegielewska Katarzyna M, Bethge Nicole, Wheaton Benjamin J, Potter Ann M, Saunders Norman R
Department of Pharmacology, University of Melbourne, Parkville, VIC 3010, Australia.
Neurosci Lett. 2009 Feb 27;451(3):232-6. doi: 10.1016/j.neulet.2009.01.021. Epub 2009 Jan 13.
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-1beta, 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.
发育性白质损伤是一种与多种长期神经障碍相关的脑部病变。炎症损伤被认为是主要的诱发事件。本研究调查了炎症、血脑屏障通透性和神经胶质细胞个体发生在白质损伤中的相对影响。在不同脑发育阶段，通过腹腔连续注射脂多糖在短尾负鼠（负鼠）中诱导全身炎症。估计外囊的白质体积。通过免疫细胞化学评估血脑屏障通透性。使用定量逆转录聚合酶链反应测量白细胞介素-1β、白细胞介素-6和环氧化酶-2的mRNA相对水平。估计小胶质细胞和星形胶质细胞数量及形态的发育变化。结果表明，对全身炎症的反应中，仅在特定时期外囊的白质减少。在相同发育阶段，血脑屏障通透性改变，出现脑部炎症反应，小胶质细胞数量增加。然而，血脑屏障通透性改变和脑部炎症反应的时期比外囊对白质损伤易感性的时期更长，这与该区域星形胶质细胞数量的发育性增加一致。因此，全身炎症后白质损伤的机制是多因素的，包括在神经胶质细胞发育的特定阶段同时发生的脑部炎症和脑屏障破坏。
