Macrophages prevent hemorrhagic infarct transformation in murine stroke models

Gliem, Michael; Mausberg, Anne K.; Lee, John-Ih; Simiantonakis, Ioannis; Rooijen, Nico van; Hartung, Hans‐Peter; Jander, Sebastian

doi:10.1002/ana.23529

Cited by 237 publications

(269 citation statements)

References 42 publications

(68 reference statements)

Supporting

Mentioning

240

Contrasting

Unclassified

Order By: Relevance

“…76 In contrast, TGFb/SMAD2 signaling in a subset of monocytes that migrate into brain 1 to 7 days after stroke reduce the BBB disruption and the rate of HT (see section below titled Delayed Hemorrhagic Transformation: Role of Neuroinflammation). 77 Early Hemorrhagic Transformation: Role of Brain Metalloproteinases Though MMP from blood has a prominent role in early BBB disruption and HT, brain-derived proteases also contribute. The role of brain-derived proteases and brain-derived molecules develops over time after stroke, becoming a major contributor to BBB disruption and HT by 24 hours.…”

Section: Early and Delayed Hemorrhagic Transformationmentioning

confidence: 99%

“…One study has shown a subset of peripheral monocytes can prevent delayed HT after ischemic stroke. 77 Within 24 hours of stroke onset, a subset of inflammatory monocytes (Ly6c hi , C-C chemokine receptor type 2 (CCR2 þ ), CX3CR1 þ ) infiltrate the infarct border via a CCR2-dependent pathway and differentiate into macrophages (Figure 2). 77 When these monocytes were depleted in a mouse stroke model, the rate of HT at both day 3 and day 7 increased.…”

Section: Delayed Hemorrhagic Transformationmentioning

confidence: 99%

“…77 Within 24 hours of stroke onset, a subset of inflammatory monocytes (Ly6c hi , C-C chemokine receptor type 2 (CCR2 þ ), CX3CR1 þ ) infiltrate the infarct border via a CCR2-dependent pathway and differentiate into macrophages (Figure 2). 77 When these monocytes were depleted in a mouse stroke model, the rate of HT at both day 3 and day 7 increased. 77 In addition, when CCR2 was blocked there was an increase in delayed HT and worsening of neurologic function.…”

Section: Delayed Hemorrhagic Transformationmentioning

confidence: 99%

“…77 When these monocytes were depleted in a mouse stroke model, the rate of HT at both day 3 and day 7 increased. 77 In addition, when CCR2 was blocked there was an increase in delayed HT and worsening of neurologic function. Bleeding occurred around thin-walled, dilated neovessels in the infarct border zone and was accompanied by a decrease in TGFb1, collagen 4, and Smad2.…”

Section: Delayed Hemorrhagic Transformationmentioning

confidence: 99%

See 3 more Smart Citations

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Jickling

Liu

Stamova

et al. 2013

J Cereb Blood Flow Metab

432

355

View full text Add to dashboard Cite

Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and treat HT are needed. In this review, we summarize studies of HT in both animals and humans. We propose that early HT (o18 to 24 hours after stroke onset) relates to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2 that damage the neurovascular unit and promote blood-brain barrier (BBB) disruption. This contrasts to delayed HT (418 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke.

show abstract

Section: Early and Delayed Hemorrhagic Transformationmentioning

confidence: 99%

Section: Delayed Hemorrhagic Transformationmentioning

confidence: 99%

Section: Delayed Hemorrhagic Transformationmentioning

confidence: 99%

Section: Delayed Hemorrhagic Transformationmentioning

confidence: 99%

See 2 more Smart Citations

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Jickling

Liu

Stamova

et al. 2013

J Cereb Blood Flow Metab

432

355

View full text Add to dashboard Cite

show abstract

“…1 These processes have been considered to mediate both beneficial and adverse effects on disease progression during the acute and subacute stages of stroke. [2][3][4] Consequently, the modulation of postischemic inflammation represents an eligible approach toward novel treatment strategies. 5 However, translational research in this field is complicated by the fact that the rodent immune system including its specific responses is only partially comparable with the human one.…”

Section: Introductionmentioning

confidence: 99%

Sterile Inflammation after Permanent Distal MCA Occlusion in Hypertensive Rats

Möller

Boltze²,

Pösel

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The pathophysiology of stroke is governed by immune reactions within and remote from the injured brain. Hypertension, a major cause and comorbidity of stroke, entails systemic vascular inflammation and may influence poststroke immune responses. This aspect is, however, underestimated in previous studies. Here we aimed to delineate the sequence of cellular inflammation after stroke in spontaneously hypertensive (SH) rats. Spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion and killed after 1 or 4 days. Immune cells of the peripheral blood and those which have infiltrated the injured brain were identified and quantified by flow cytometry. The spatial distribution of myeloid cells and T lymphocytes, and the infarct volume were assessed by histology. We observed a concerted infiltration of immune cells into the ischemic brain of SH rats. At day 1, primarily neutrophils, monocytes, macrophages, and myeloid dendritic cells entered the brain, whereas the situation at day 4 was dominated by microglia, macrophages, lymphatic dendritic cells, and T cells. Postischemic inflammation did not cause secondary tissue damage during the subacute stage of experimental stroke in SH rats. Considering the intrinsic vascular pathology of SH rats, our study validates this strain for further translational research in poststroke inflammation.

show abstract

The Innate Immune System After Ischemic Injury

2014

View full text Add to dashboard Cite

troke is the third most common cause of death in the United States, and most strokes are due to thrombotic or embolic complications of atherosclerosis. One in four strokes are recurrent events, 1 highlighting that both primary and secondary prevention are currently insufficient. 2 While it is increasingly agreed that innate immune cells importantly contribute to atherosclerosis and its ischemic complications, the role of leukocytes, their subsets, sources, and fates after stroke are incompletely understood. Ischemic stroke and myocardial infarction (MI) have in common that the sustained tissue injury is sterile and that it is caused by a lack of oxygen. Distinct differences include the phenotype of injured cells and tissues as well as the nature and timing of signals from ischemic brain and heart. Because both MI and ischemic stroke are caused by atherosclerosis, we suspect that there are many similarities. Therefore, the comparison of the immune response to these 2 most deadly complications of vascular disease may be useful. In our review, we highlight open questions regarding the systemic innate immune response after stroke, relating them to recent insight obtained after MI.

show abstract

Macrophages prevent hemorrhagic infarct transformation in murine stroke models

Cited by 237 publications

References 42 publications

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Sterile Inflammation after Permanent Distal MCA Occlusion in Hypertensive Rats

The Innate Immune System After Ischemic Injury

Contact Info

Product

Resources

About