Age-Dependent Microglial Activation in Immature Brains After Hypoxia- Ischemia

Author(s): Peter Ferrazzano, Vishal Chanana, Kutluay Uluc, Emin Fidan, Erinc Akture, Douglas B. Kintner, Pelin Cengiz, Dandan Sun

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 12 , Issue 3 , 2013

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In the present study, we tested whether the ongoing differentiation of microglia in the immature brain results in more robust microglial activation and pro-inflammatory responses than juvenile brains following hypoxia-ischemia (HI). Under normoxic conditions, microglial activation profiles were assessed in postnatal day 9 and postnatal day 30 mice (P9 and P30) by analyzing relative expression levels of CD45 in CD11b+/CD45+ microglia/macrophages. Flow cytometry analysis revealed that the hippocampi of P9 and P30 brains exhibited higher levels of CD45 expression in CD11b+/CD45+ cells than in the cortex and striatum. In response to HI, there was an early increase in number of CD11b+/CD45+ microglia/macrophages in the ipsilateral hippocampus of P9 mice. These cells transformed from a “ramified” to an “amoeboid” morphology in the CA1 region, which was accompanied by a loss of microtubule-associated protein 2 immunostaining in this brain region. The peak response of microglial activation in the ipsilateral hippocampus of P9 mice occurred on day 2 post-HI, which was in contrast to a delayed and persistent microglial activation in the cortex and striatum (peak on day 9 post-HI). P9 brains demonstrated a 2-3 fold greater increase in microglia counts than P30 brains in each region (hippocampus, cortex, and striatum) during day 1-17 post-HI. P9 brains also showed more robust expression of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β) than P30 brains. Taken together, compared to P30 mice, P9 mice demonstrated differences in microglial activation and pro-inflammatory responses after HI, which may be important in brain damage and tissue repair.

Keywords: Microglia, neonatal hypoxic ischemia, inflammation, apoptosis.

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Article Details

Year: 2013
Page: [338 - 349]
Pages: 12
DOI: 10.2174/1871527311312030007
Price: $65

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