CNS & Neurological Disorders - Drug Targets

(Formerly Current Drug Targets - CNS & Neurological Disorders)

Stephen D. Skaper  
Department of Pharmaceutical and Pharmacological Sciences
University of Padova


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 and Dandan Sun

Affiliation: Department of Pediatrics, University of Wisconsin Medical School, T517 Waisman Center, 1500 Highland Ave., Madison, WI 53705, USA.


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

Page: [338 - 349]
Pages: 12
DOI: 10.2174/1871527311312030007