Noggin improves ischemic brain tissue repair and promotes alternative activation of microglia in mice

Jin A. Shin, Soo Mee Lim, Sae Im Jeong, Jihee Lee Kang, Eun Mi Park

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

We previously reported that bone morphogenetic proteins (BMPs) and their endogenous antagonist noggin are expressed in the brain weeks after an ischemic insult. Here, to define their roles in ischemic brain tissue repair and remodeling, we infused recombinant BMP7 or noggin into the ipsilateral ventricle of mice for 2. weeks starting 2. weeks after transient middle cerebral artery occlusion (MCAO). Four weeks after MCAO, we measured ischemic brain volume, functional recovery, and molecules related to neurogenesis and angiogenesis such as synaptophysin, GAP-43, and VEGF. Noggin-treated mice but not BMP7-treated mice showed preserved ipsilateral brain volume and reduced neurological deficits compared with artificial cerebrospinal fluids (aCSF)-treated mice. Noggin treatment also decreased glial scar thickness, increased levels of GAP-43 and VEGF protein, and increased the number of Iba1-positive activated microglia in the ipsilateral brain. Furthermore, noggin treatment decreased M1 markers (IL-1β, TNF-α, IL-12, CCL2 and CD86) and increased M2 markers (IL-1ra, IL-10, arginase 1, CD206 and Ym1) of activated microglia, suggesting a shift from M1 to M2 phenotypes. These results suggest that noggin improves functional recovery from ischemic stroke and enhances alternatively activated microglia, thereby promoting tissue repair and remodeling.

Original languageEnglish
Pages (from-to)143-154
Number of pages12
JournalBrain, Behavior, and Immunity
Volume40
DOIs
StatePublished - Aug 2014

Keywords

  • BMPs
  • Brain atrophy
  • Functional recovery
  • Glial scar
  • Ischemic stroke
  • M2 phenotype
  • Microglia
  • Neurorestorative therapy
  • Noggin
  • Repair process

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