Open AccessAmoeboid Microglia in the Periventricular White Matter Induce Oligodendrocyte Damage through Expression of Proinflammatory Cytokines via MAP Kinase Signaling Pathway in Hypoxic Neonatal Rats
Author(s) -
Deng YiYu,
Lu Jia,
Sivakumar Viswanathan,
Ling Eng Ang,
Kaur Charanjit
Publication year - 2008
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2008.00138.x
Subject(s) - proinflammatory cytokine , microglia , tumor necrosis factor alpha , hypoxia (environmental) , brain damage , biology , signal transduction , microbiology and biotechnology , medicine , immunology , pathology , inflammation , chemistry , neuroscience , organic chemistry , oxygen
Hypoxic injury in the perinatal period results in periventricular white matter (PWM) lesions with axonal damage and oligodendroglial loss. It also alters macrophage function by perpetuating expression of inflammatory mediators. Relevant to this is the preponderance of amoeboid microglial cells (AMC) characterized as active macrophages in the developing PWM. This study aimed to determine if AMC produce proinflammatory cytokines that may be linked to the oligodendroglial loss observed in hypoxic PWM damage (PWMD). Wistar rats (1 day old) were subjected to hypoxia, following which upregulated expression of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), TNF receptor 1 (TNF‐R 1 ) and IL‐1 receptor 1 (IL‐1R 1 ) was observed. This was coupled with apoptosis and expression of TNF‐R 1 and IL‐1R 1 in oligodendrocytes. Primary cultured microglial cells subjected to hypoxia (3% oxygen, 5% CO 2 and 92% nitrogen) showed enhanced expression of TNF‐α and IL‐1β. Furthermore, mitogen‐activated protein (MAP) kinase signaling pathway was involved in the expression of TNF‐α and IL‐1β in microglia subjected to hypoxia. Our results suggest that following a hypoxic insult, microglial cells in the neonatal rats produce inflammatory cytokines such as TNF‐α and IL‐1β via MAP kinase signaling pathway. These cytokines are detrimental to oligodendrocytes resulting in PWM lesion.