Role of Erythrocyte CD47 in Intracerebral Hematoma Clearance

Ni, Wei; Mao, Shanshan; Xi, Guohua; Keep, Richard F.; Hua, Ya

doi:10.1161/strokeaha.115.010920

Cited by 74 publications

(63 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent research has studied microglia/macrophage activation and polarization in several neurological conditions, including brain ischemia [10, 11, 16–18]. However, the polarized microglia/macrophage activation after ICH has not been well studied [36, 37]. The present study reveals the time course of polarized microglia/macrophage activation after ICH, which should provide a solid basis for further investigation to microglia/macrophage-mediated inflammatory injury and repair after ICH.…”

Section: Discussionmentioning

confidence: 58%

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

Wan

Cheng

Jin

et al. 2016

Transl. Stroke Res.

Self Cite

128

103

View full text Add to dashboard Cite

Polarized microglia play a dual (beneficial/detrimental) role in neurological diseases. However, the status and the factors that modulate microglia polarization in intracerebral hemorrhage (ICH) remain unclear. In the present study, we investigated the role of protease-activated receptor-1 (PAR-1, a thrombin receptor) in ICH-induced microglia polarization in mice. Male wild-type (WT) and PAR-1 knockout (PAR-1 KO) mice received an infusion of 30-μL autologous blood or saline into the right basal ganglia. Mice were euthanized at different time points and the brains were used for Western blotting and immunohistochemistry. Some mice had magnetic resonance imaging. We found that ICH induced microglia activation and polarization. M1 phenotypic markers were markedly increased and reached a peak as early as 4 h, remained high at 3 days and decreased 7 days after ICH. M2 phenotypic markers were upregulated later than M1 markers reaching a peak at day 1 and declining by day 7 after ICH. PAR-1 was upregulated after ICH and expressed in the neurons and microglia. ICH induced less brain swelling and neuronal death in PAR-1 KO mice, and this was associated with less M1 polarization and reduced proinflammatory cytokine levels in the brain. In conclusion, these results suggest that polarized microglia occur dynamically after ICH and that PAR-1 plays a role in the microglia activation and polarization.

show abstract

Section: Discussionmentioning

confidence: 58%

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

Wan

Cheng

Jin

et al. 2016

Transl. Stroke Res.

Self Cite

128

103

View full text Add to dashboard Cite

show abstract

“…Phagocytosis of erythrocytes by microglia/macrophages has a role in hematoma clearance after ICH 7 . The current study examined the natural time course of CD47 expression in the hematoma in a swine ICH model and found that CD47 levels in the clot decrease with time.…”

Section: Discussionmentioning

confidence: 99%

“…On normal RBCs, CD47 inhibits phagocytosis via interaction with an inhibitory receptor, signal regulatory protein alpha (SIRPα), on phagocytes. Our recent study showed that CD47 on RBCs has a role in clot removal following ICH 7 .…”

Section: Introductionmentioning

confidence: 92%

Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Cao

Zheng

Hua

et al. 2016

Stroke

Self Cite

104

View full text Add to dashboard Cite

Background and Purpose Hematoma clearance occurs in the days after intracerebral hemorrhage (ICH) and has not been well studied. In the current study, we examined changes in the hematoma in a piglet ICH model. The effect of deferoxamine on hematoma was also examined. Methods The ICH model was induced by an injection of autologous blood into the right frontal lobe of piglets. First, a natural time course of hematoma changes up to 7 days was determined. Second, the effect of deferoxamine on hematoma changes was examined. Hemoglobin and membrane attack complex levels in the hematoma were examined by enzyme-linked immunosorbent assay. Immunohistochemistry and Western blotting was used to examine CD47 (a regulator of erythrophagocytosis), CD163 (a hemoglobin scavenger receptor) and heme oxygenase-1 (a heme degradation enzyme) in the clot. Results After ICH, there was a reduction in red blood cell diameter within the clot with time. This was accompanied by membrane attack complex accumulation and decreased hemoglobin levels. Erythrophagocytosis occurred in the hematoma and this was associated with reduced clot CD47 levels. Activated macrophages/microglia were CD163 and hemeoxygenase-1 positive and these accumulated in the clot with time. Deferoxamine treatment attenuated the process of hematoma resolution by reducing member attack complex formation and inhibiting CD47 loss in the clot. Conclusion These results indicate that membrane attack complex and erythrophagocytosis contribute to hematoma clearance after ICH, which can be altered by deferoxamine treatment.

show abstract

“…In the third part, WT or PAR-1 KO mice received an intracerebral injection of thrombin (0.4U) in saline or saline alone (n=7 per group). Based on our prior study on the variance in ICH-induced brain swelling in mice 14 , we estimated that an n=7 per experimental group would be able to detect a 50% reduction in brain swelling with greater than 80% power. All mice were euthanized at 24 hours or 72 hours after T2-weighted magnetic resonance imaging (MRI) and behavioral testing.…”

Section: Methodsmentioning

confidence: 99%

“…Brain swelling calculation was based upon seven every other sections whose center was the anterior commissure layer. The value was: volume of (ipsilateral hemisphere- contralateral hemisphere)/volume of contralateral hemisphere×100 % 12, 14 .…”

Section: Methodsmentioning

confidence: 99%

Role of Lipocalin-2 in Thrombin-Induced Brain Injury

Mao

Keep

et al. 2016

Stroke

Self Cite

View full text Add to dashboard Cite

Background and Purpose Thrombin and lipocalin-2 (LCN2) contribute to intracerebral hemorrhage-induced brain injury. Thrombin-induced brain damage is partially through a thrombin receptor, protease-activated receptor-1 (PAR-1). LCN2 is involved in cellular iron transport and neuroinflammation. The present study investigated the role of LCN2 in thrombin-induced brain injury. Methods There was three parts in this study. First, male adult C57BL/6 wild type (WT) or LCN2 knockout (LCN2 KO) mice had an intracaudate injection of thrombin (0.4U) or saline. Second, LCN2 KO mice had an injection of thrombin (0.4U) with recombinant mouse LCN2 protein (1µg) into the right caudate. Third, PAR-1 KO or WT mice had an intracaudate injection of thrombin or saline. All mice had T2-weighted magnetic resonance imaging and behavioral tests. Brains were used for histology, immunohistochemistry and Western blotting. Results Intracerebral thrombin injection caused LCN2 upregulation and brain injury in mice. Thrombin-induced brain swelling, blood-brain barrier disruption, neuronal death and neurologic deficits were markedly less in LCN2 KO mice (p<0.05) and were exacerbated by exogenous LCN2 co-injection. In addition, thrombin injection resulted in less LCN2 expression and brain injury in PAR-1 KO mice. Conclusions Thrombin upregulates LCN2 through PAR-1 activation and causes brain damage.

show abstract

Role of Erythrocyte CD47 in Intracerebral Hematoma Clearance

Cited by 74 publications

References 41 publications

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1

Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Role of Lipocalin-2 in Thrombin-Induced Brain Injury

Contact Info

Product

Resources

About