Alternatively activated brain-infiltrating macrophages facilitate recovery from collagenase-induced intracerebral hemorrhage.
BACKGROUND
Intracerebral hemorrhage (ICH) is one of the major causes of stroke. After onset of ICH, massive infiltration of macrophages is detected in the peri-hematoma regions. Still, the function of these macrophages in ICH has not been completely elucidated.


RESULTS
In a collagenase-induced ICH model, CX3CR1(+) macrophages accumulated in the peri-hematoma region. Characterization of these macrophages revealed expression of alternatively activated (M2) macrophage markers. In the macrophage-depleted mice, ICH-induced brain lesion volume was larger and neurological deficits were more severe compared to those of control mice, indicating a protective role of these macrophages in ICH. In the ICH-injured brain, mannose receptor-expressing macrophages increased at a delayed time point after ICH, indicating M2 polarization of the brain-infiltrating macrophages in the brain microenvironment. To explore this possibility, bone marrow-derived macrophages (BMDM) were co-cultured with mouse brain glial cells and then tested for activation phenotype. Upon co-culture with glia, the number of mannose receptor-positive M2 macrophages was significantly increased. Furthermore, treatment with glia-conditioned media increased the number of BMDM of M2 phenotype.


CONCLUSIONS
In this study, our data suggest that brain-infiltrating macrophages after ICH are polarized to the M2 phenotype by brain glial cells and thereby contribute to recovery from ICH injury.
Department of Neuroscience and Dental Research Institute, School of Dentistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Hyunjung
H
Min
Department of Neuroscience and Dental Research Institute, School of Dentistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Yong Ho
YH
Jang
Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, 02447, Korea.
Ik-Hyun
IH
Cho
Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 42988, Korea.
Seong-Woon
SW
Yu
Department of Neuroscience and Dental Research Institute, School of Dentistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea. sjlee87@snu.ac.kr.
Sung Joong
SJ
Lee
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D001921:Brain / Q000473:pathology*; D016764:Cell Polarity; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000473:pathology*; D017364:Collagenases; D006406:Hematoma / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism; D010641:Phenotype; D012995:Solubility
D017364:Collagenases
Immune response; Macrophages; Wound healing