title: Age-dependent microglial activation in immature brains after hypoxia- ischemia.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, 1500 Highland Ave., Madison, WI 53705, USA. ferrazzano@pediatrics.wisc.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Ferrazzano
authors.forename: Vishal
authors.initials: V
authors.lastname: Chanana
authors.forename: Kutluay
authors.initials: K
authors.lastname: Uluc
authors.forename: Emin
authors.initials: E
authors.lastname: Fidan
authors.forename: Erinc
authors.initials: E
authors.lastname: Akture
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kintner
authors.forename: Pelin
authors.initials: P
authors.lastname: Cengiz
authors.forename: Dandan
authors.initials: D
authors.lastname: Sun
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D053583:Interleukin-1beta; D008869:Microtubule-Associated Proteins; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D053148:Caspase 3