Temporal Changes in Cell Marker Expression and Cellular Infiltration in a Controlled Cortical Impact Model in Adult Male C57BL/6 Mice

Jin, Xin; Ishii, Hiroshi; Bai, Zhongbin; Itokazu, Takahide; Yamashita, Toshio

doi:10.1371/journal.pone.0041892

Cited by 175 publications

(189 citation statements)

References 44 publications

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“…By differential expression of CD45, the infiltrating MMs (CD45 high /CD11b þ ) have been distinguished from the resident microglia (CD45 low /CD11b þ ). [25][26][27] We found that the CD45 high /CD11b þ population was absent in the naive brain (data not shown) and the contralateral hemisphere, but appears in the ipsilateral hemisphere ( Figure 4B). The MM (CD45 high /CD11b þ ) population was subjected to the analysis post ischemia.…”

Section: Ly-6cmentioning

confidence: 75%

Role of Spleen-Derived Monocytes/Macrophages in Acute Ischemic Brain Injury

Kim

Yang

Beltran

et al. 2014

J Cereb Blood Flow Metab

161

204

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Monocytes/macrophages (MMs), mononuclear phagocytes, have been implicated in stroke-induced inflammation and injury. However, the presence of pro-inflammatory Ly-6Chigh and antiinflammatory Ly-6Clow monocyte subsets raises uncertainty regarding their role in stroke pathologic assessment. With recent identification of the spleen as an immediate reservoir of MMs, this current study addresses whether the spleen-derived MMs are required for stroke pathologic assessment. We observed that the spleen was contracted in poststroke animals and the contraction was accompanied by decreased number of Ly-6Chigh and Ly-6Clow subsets in the spleen. The deployment of these subsets from the spleen temporally coincided with respective increases in the ischemic brain. Compared to mice with the spleen, mice receiving a splenectomy just before the stroke displayed less accumulation of Ly-6Chigh and Ly-6Clow MMs in the brain. Despite the reduced accumulation of both subsets, infarct size and swelling were not reduced in the asplenic mice. The dissociative findings of infarct size and extent of MM infiltration in the postischemic brain indicate minimal involvement of spleen-derived total MMs in acute infarct development. Selective Ly-6Chigh or Ly-6Clow MM targeting is suggested to address the contribution of the individual subset to acute stroke pathologic assessment.

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Section: Ly-6cmentioning

confidence: 75%

Role of Spleen-Derived Monocytes/Macrophages in Acute Ischemic Brain Injury

Kim

Yang

Beltran

et al. 2014

J Cereb Blood Flow Metab

161

204

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“…These data support other studies that evaluated macrophage and immune cell infiltration dynamics in TBI models. 30,31 Due to technical limitations when combining internalization staining protocols for M1-/M2-like markers with CD11b/CD45 cell surface markers, it was not possible to determine whether the infiltrating macrophages after were more M1-or M2-like polarized, but the peak in infiltration corresponded with high expression levels of both M1-and M2-like protein markers in this study.…”

Section: Fig 7 (Continued)mentioning

confidence: 90%

Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury

Kumar

Álvarez‐Croda

Stoica

et al. 2016

Journal of Neurotrauma

275

271

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Activated microglia and macrophages exert dual beneficial and detrimental roles after central nervous system injury, which are thought to be due to their polarization along a continuum from a classical pro-inflammatory M1-like state to an alternative anti-inflammatory M2-like state. The goal of the present study was to analyze the temporal dynamics of microglia/macrophage polarization within the lesion micro-environment following traumatic brain injury (TBI) using a moderate-level controlled cortical impact (CCI) model in mice. We performed a detailed phenotypic analysis of M1-and M2-like polarized microglia/macrophages, as well as nicotinamide adenine dinucleotide phosphate oxidase (NOX2) expression, through 7 days post-injury using real-time polymerase chain reaction (qPCR), flow cytometry and image analyses. We demonstrated that microglia/macrophages express both M1-and M2-like phenotypic markers early after TBI, but the transient up-regulation of the M2-like phenotype was replaced by a predominant M1-or mixed transitional (Mtran) phenotype that expressed high levels of NOX2 at 7 days post-injury. The shift towards the M1-like and Mtran phenotype was associated with increased cortical and hippocampal neurodegeneration. In a follow up study, we administered a selective NOX2 inhibitor, gp91ds-tat, to CCI mice starting at 24 h post-injury to investigate the relationship between NOX2 and M1-like/Mtran phenotypes. Delayed gp91ds-tat treatment altered M1-/M2-like balance in favor of the anti-inflammatory M2-like phenotype, and significantly reduced oxidative damage in neurons at 7 days post-injury. Therefore, our data suggest that despite M1-like and M2-like polarized microglia/macrophages being activated after TBI, the early M2-like response becomes dysfunctional over time, resulting in development of pathological M1-like and Mtran phenotypes driven by increased NOX2 activity.

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“…This staining protocol was reported previously as a reproducible method for the identification of macrophage populations; however, it does not exclude some subpopulations of dendritic cells (97,98). Intraperitoneal injection of P. gingivalis (HK-W50) induced a similar M1/M2 macrophage ratio in the peritoneal cavity as that found in gingival tissue.…”

Section: Figurementioning

confidence: 99%

Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

Lam

O'Brien-Simpson

Lenzo

et al. 2014

The Journal of Immunology

119

140

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The role of the macrophage in the immunopathology of periodontitis has not been well defined. In this study, we show that intraoral inoculation of mice with Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a significant increase in F4/80+ macrophages in gingival and submandibular lymph node tissues. Macrophage depletion using clodronate-liposomes resulted in a significant reduction in F4/80+ macrophage infiltration of gingival and submandibular lymph node tissues and significantly (p < 0.01) less P. gingivalis–induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In both mouse strains, the P. gingivalis–specific IgG Ab subclass and serum cytokine [IL-4, IL-10, IFN-γ, and IL-12 (p70)] responses were significantly (p < 0.01) lower in the macrophage-depleted groups. Macrophage depletion resulted in a significant reduction in the level of P. gingivalis infection, and the level of P. gingivalis infection was significantly correlated with the level of alveolar bone resorption. M1 macrophages (CD86+), rather than M2 macrophages (CD206+), were the dominant macrophage phenotype of the gingival infiltrate in response to P. gingivalis infection. P. gingivalis induced a significant (p < 0.01) increase in NO production and a small increase in urea concentration, as well as a significant increase in the secretion of IL-1β, IL-6, IL-10, IL-12 (p70), eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage inflammatory protein-α and -β, and TNF-α in isolated murine macrophages. In conclusion, P. gingivalis infection induced infiltration of functional/inflammatory M1 macrophages into gingival tissue and alveolar bone resorption. Macrophage depletion reduced P. gingivalis infection and alveolar bone resorption by modulating the host immune response.

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Temporal Changes in Cell Marker Expression and Cellular Infiltration in a Controlled Cortical Impact Model in Adult Male C57BL/6 Mice

Cited by 175 publications

References 44 publications

Role of Spleen-Derived Monocytes/Macrophages in Acute Ischemic Brain Injury

Role of Spleen-Derived Monocytes/Macrophages in Acute Ischemic Brain Injury

Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury

Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

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