TY - JOUR
T1 - Noggin improves ischemic brain tissue repair and promotes alternative activation of microglia in mice
AU - Shin, Jin A.
AU - Lim, Soo Mee
AU - Jeong, Sae Im
AU - Kang, Jihee Lee
AU - Park, Eun Mi
N1 - Funding Information:
This study was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) ( 2010-0011353 and 2012R1A5A2A32671867 ).
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - BMPs
KW - Brain atrophy
KW - Functional recovery
KW - Glial scar
KW - Ischemic stroke
KW - M2 phenotype
KW - Microglia
KW - Neurorestorative therapy
KW - Noggin
KW - Repair process
UR - http://www.scopus.com/inward/record.url?scp=84904122170&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2014.03.013
DO - 10.1016/j.bbi.2014.03.013
M3 - Article
C2 - 24704569
AN - SCOPUS:84904122170
SN - 0889-1591
VL - 40
SP - 143
EP - 154
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -