Open AccessMicroglia‐Derived Macrophage Colony Stimulating Factor Promotes Generation of Proinflammatory Cytokines by Astrocytes in the Periventricular White Matter in the Hypoxic Neonatal Brain
Author(s) -
Deng Yi Yu,
Lu Jia,
Ling EngAng,
Kaur Charanjit
Publication year - 2010
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.1750-3639.2010.00387.x
Subject(s) - proinflammatory cytokine , microglia , astrocyte , tumor necrosis factor alpha , neuroglia , biology , inflammation , cytokine , pathology , microbiology and biotechnology , immunology , endocrinology , medicine , central nervous system
Inflammation in the periventricular white matter (PWM) of hypoxic neonatal brain causes myelination disturbances. In this connection, macrophage colony‐stimulating factor (M‐CSF) has been reported to regulate release of proinflammatory cytokines that may be linked to PWM damage. We sought to determine if M‐CSF derived from amoeboid microglial cells (AMC) would promote proinflammatory cytokine production by astrocytes in the PWM following hypoxic exposure, and, if so, whether it is associated with axon degeneration and myelination disturbances. In 1‐day hypoxic rats, expression of M‐CSF was upregulated in AMC. This was coupled with increased expression of CSF‐1 receptor, tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in astrocytes, and TNF‐receptor 1 and IL‐receptor 1 on the axons. Neurofilament‐200 immunopositive axons and myelin basic protein immunopositive processes appeared to undergo disruption in 14‐days hypoxic rats. By electron microscopy, some axons showed degenerative changes affecting the microtubules and myelin sheath. Primary cultured microglial cells subjected to hypoxia showed enhanced release of M‐CSF. Remarkably, primary cultured astrocytes treated with conditioned‐medium derived from hypoxic microglia or M‐CSF exhibited increased production of TNF‐α and IL‐1β. Our results suggest that AMC‐derived M‐CSF promotes astrocytes to generate proinflammatory cytokines, which may be involved in axonal damage following a hypoxic insult.