CX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice

Stefano Fumagalli, Carlo Perego, Fabrizio Ortolano, Maria Grazia De Simoni

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of CX3CR1 deletion in ischemic (30′ MCAo) mice on: (1) brain infarct size; (2) microglia dynamism and morphology; (3) expression of markers of microglia/macrophages (M/M) activation and polarization. We observed smaller infarcts in cx3cr1-/- (26.42 ± 7.41 mm3, mean ± sd) compared to wild type (36.29 ± 11.57) and cx3cr1-/+ (34.49 ± 8.91) mice. We longitudinally analyzed microglia by in vivo two-photon microscopy before, 1 and 24 h after transient ischemia. Microglia were stationary in both cx3cr1-/- and cx3cr1-/+ mice throughout the study. In cx3cr1-/- mice, they displayed a significantly higher number of ramifications >10 μm at baseline and at 24 h after ischemia compared to cx3cr1-/+ mice, indicating that CX3CR1 deficiency impaired the development of microglia hypertrophic/amoeboid morphology. At 24 h after ischemia, we performed post mortem quantitative immunohistochemistry for different M/M markers. In cx3cr1-/- immunoreactivity for CD11b (M/M activation) and for CD68 (associated with phagocytosis) were decreased, while that for CD45high (macrophage and leukocyte recruitment) was increased. In addition, immunoreactivity for Ym1 (M2 polarization) was enhanced, while that for iNOS (M1) was decreased. Our data show that in cx3cr1-/- mice protection from ischemia at early time points after injury is associated with a protective inflammatory milieu, characterized by the promotion of M2 polarization markers.

Original languageEnglish
Pages (from-to)827-842
Number of pages16
JournalGLIA
Volume61
Issue number6
DOIs
Publication statusPublished - Jun 2013

Fingerprint

Microglia
Ischemia
Macrophage Activation
Macrophages
Chemokine CX3CL1
Nervous System Diseases
Photons
Phagocytosis
Microscopy
Leukocytes
Immunohistochemistry
Wounds and Injuries
Brain

Keywords

  • Alternative activation
  • CX3CR1
  • Fractalkine
  • Microglia
  • Two-photon microscopy

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

CX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice. / Fumagalli, Stefano; Perego, Carlo; Ortolano, Fabrizio; De Simoni, Maria Grazia.

In: GLIA, Vol. 61, No. 6, 06.2013, p. 827-842.

Research output: Contribution to journalArticle

@article{c5624d549437416da451e597c2f3b60a,
title = "CX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice",
abstract = "The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of CX3CR1 deletion in ischemic (30′ MCAo) mice on: (1) brain infarct size; (2) microglia dynamism and morphology; (3) expression of markers of microglia/macrophages (M/M) activation and polarization. We observed smaller infarcts in cx3cr1-/- (26.42 ± 7.41 mm3, mean ± sd) compared to wild type (36.29 ± 11.57) and cx3cr1-/+ (34.49 ± 8.91) mice. We longitudinally analyzed microglia by in vivo two-photon microscopy before, 1 and 24 h after transient ischemia. Microglia were stationary in both cx3cr1-/- and cx3cr1-/+ mice throughout the study. In cx3cr1-/- mice, they displayed a significantly higher number of ramifications >10 μm at baseline and at 24 h after ischemia compared to cx3cr1-/+ mice, indicating that CX3CR1 deficiency impaired the development of microglia hypertrophic/amoeboid morphology. At 24 h after ischemia, we performed post mortem quantitative immunohistochemistry for different M/M markers. In cx3cr1-/- immunoreactivity for CD11b (M/M activation) and for CD68 (associated with phagocytosis) were decreased, while that for CD45high (macrophage and leukocyte recruitment) was increased. In addition, immunoreactivity for Ym1 (M2 polarization) was enhanced, while that for iNOS (M1) was decreased. Our data show that in cx3cr1-/- mice protection from ischemia at early time points after injury is associated with a protective inflammatory milieu, characterized by the promotion of M2 polarization markers.",
keywords = "Alternative activation, CX3CR1, Fractalkine, Microglia, Two-photon microscopy",
author = "Stefano Fumagalli and Carlo Perego and Fabrizio Ortolano and {De Simoni}, {Maria Grazia}",
year = "2013",
month = "6",
doi = "10.1002/glia.22474",
language = "English",
volume = "61",
pages = "827--842",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - CX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice

AU - Fumagalli, Stefano

AU - Perego, Carlo

AU - Ortolano, Fabrizio

AU - De Simoni, Maria Grazia

PY - 2013/6

Y1 - 2013/6

N2 - The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of CX3CR1 deletion in ischemic (30′ MCAo) mice on: (1) brain infarct size; (2) microglia dynamism and morphology; (3) expression of markers of microglia/macrophages (M/M) activation and polarization. We observed smaller infarcts in cx3cr1-/- (26.42 ± 7.41 mm3, mean ± sd) compared to wild type (36.29 ± 11.57) and cx3cr1-/+ (34.49 ± 8.91) mice. We longitudinally analyzed microglia by in vivo two-photon microscopy before, 1 and 24 h after transient ischemia. Microglia were stationary in both cx3cr1-/- and cx3cr1-/+ mice throughout the study. In cx3cr1-/- mice, they displayed a significantly higher number of ramifications >10 μm at baseline and at 24 h after ischemia compared to cx3cr1-/+ mice, indicating that CX3CR1 deficiency impaired the development of microglia hypertrophic/amoeboid morphology. At 24 h after ischemia, we performed post mortem quantitative immunohistochemistry for different M/M markers. In cx3cr1-/- immunoreactivity for CD11b (M/M activation) and for CD68 (associated with phagocytosis) were decreased, while that for CD45high (macrophage and leukocyte recruitment) was increased. In addition, immunoreactivity for Ym1 (M2 polarization) was enhanced, while that for iNOS (M1) was decreased. Our data show that in cx3cr1-/- mice protection from ischemia at early time points after injury is associated with a protective inflammatory milieu, characterized by the promotion of M2 polarization markers.

AB - The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of CX3CR1 deletion in ischemic (30′ MCAo) mice on: (1) brain infarct size; (2) microglia dynamism and morphology; (3) expression of markers of microglia/macrophages (M/M) activation and polarization. We observed smaller infarcts in cx3cr1-/- (26.42 ± 7.41 mm3, mean ± sd) compared to wild type (36.29 ± 11.57) and cx3cr1-/+ (34.49 ± 8.91) mice. We longitudinally analyzed microglia by in vivo two-photon microscopy before, 1 and 24 h after transient ischemia. Microglia were stationary in both cx3cr1-/- and cx3cr1-/+ mice throughout the study. In cx3cr1-/- mice, they displayed a significantly higher number of ramifications >10 μm at baseline and at 24 h after ischemia compared to cx3cr1-/+ mice, indicating that CX3CR1 deficiency impaired the development of microglia hypertrophic/amoeboid morphology. At 24 h after ischemia, we performed post mortem quantitative immunohistochemistry for different M/M markers. In cx3cr1-/- immunoreactivity for CD11b (M/M activation) and for CD68 (associated with phagocytosis) were decreased, while that for CD45high (macrophage and leukocyte recruitment) was increased. In addition, immunoreactivity for Ym1 (M2 polarization) was enhanced, while that for iNOS (M1) was decreased. Our data show that in cx3cr1-/- mice protection from ischemia at early time points after injury is associated with a protective inflammatory milieu, characterized by the promotion of M2 polarization markers.

KW - Alternative activation

KW - CX3CR1

KW - Fractalkine

KW - Microglia

KW - Two-photon microscopy

UR - http://www.scopus.com/inward/record.url?scp=84876486923&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876486923&partnerID=8YFLogxK

U2 - 10.1002/glia.22474

DO - 10.1002/glia.22474

M3 - Article

C2 - 23440897

AN - SCOPUS:84876486923

VL - 61

SP - 827

EP - 842

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 6

ER -