Murine models of inflammatory bleeding
| Murine models used . | Description . | Role of platelets in preventing hemorrhage . | Role of platelets in leukocyte recruitment . | Clinical relevance . | Reference . |
|---|---|---|---|---|---|
| Cerebral IRI-tMCAO | Transient occlusion of the middle cerebral artery is realized by introducing a filament into the artery | Conflicting data, with thrombocytopenia being associated with microbleeds in one study, infarct protection in another | Unclear | Secondary hemorrhage is a highly relevant and dreaded complication of ischemic stroke | 30,36 |
| Acute lung injury (acid-induced) | Alveolar instillation of hydrochloric acid, causing sterile inflammation and injury | No data available | Leukocyte recruitment depends on presence of platelets | Pulmonary hemorrhage in the context of acute lung injury is a relevant and challenging clinical scenario | 37 |
| Acute lung injury (LPS-induced) | Alveolar LPS instillation, mimicking infectious causes of acute lung injury | Severe alveolar bleeding observed in thrombocytopenia | Leukocyte recruitment not affected by thrombocytopenia | See above | 36,38,39 |
| Dermal rpA | Model of immune complex–mediated acute inflammatory tissue injury by antigen/antibody coinjection | Severe cutaneous bleeding observed in thrombocytopenia | Platelets orchestrate leukocyte recruitment in this model | Immune complex–mediated bleeding of minor clinical relevance | 36,40 |
| Pulmonary rpA | See above; intracheal instillment | No effect reported | No effect reported | Immune complex–mediated bleeding of minor clinical relevance | 41 |
| Peritoneal rpA | See above; intraperitoneal instillment | Severe abdominal bleeding in thrombocytopenia | Reduced leukocyte recruitment in thrombocytopenia | Immune complex–mediated bleeding of minor clinical relevance | 42 |
| Tumor microvasculature | Induction of local malignoma and subsequent assessment of tumor microvasculature | Thrombocytopenia associated with hemorrhage, might be associated with higher efficiency of chemotherapy | No effect reported | Malignancy associated bleeding is a relevant clinical problem particularly in advanced tumor stages | 43,44 |
| Peritonitis (LPS-induced) | Injection of LPS into the peritoneal cavity | Inconclusive results, thrombocytopenia might result in microbleeding | Platelet depletion severely reduces leukocyte recruitment | Infection-associated peritoneal hemorrhage of minor relevance | 39,45 |
| UV-B induced dermal injury | UV-B exposure of the skin | Thrombocytopenia causes bleeding | No effect reported | Of minor clinical relevance | 46 |
| Cremasteric inflammation (LPS- or cytokine-induced) | LPS/cytokines are injected intrascrotally and the cremaster muscle is exposed for imaging/whole mount microscopy | Platelets are required to prevent microbleeds | Platelets are crucial for leukocyte recruitment in this model | Diffuse muscle bleeding is rather rare and of minor clinical importance | 38,47 |
| Inflammatory colitis | Oral administration of DSS | Platelets are required to prevent microbleeds | No data available | Major relevance of hemodynamically relevant intestinal bleeding in patients with inflammatory bowel diseases | 48 |
| Murine models used . | Description . | Role of platelets in preventing hemorrhage . | Role of platelets in leukocyte recruitment . | Clinical relevance . | Reference . |
|---|---|---|---|---|---|
| Cerebral IRI-tMCAO | Transient occlusion of the middle cerebral artery is realized by introducing a filament into the artery | Conflicting data, with thrombocytopenia being associated with microbleeds in one study, infarct protection in another | Unclear | Secondary hemorrhage is a highly relevant and dreaded complication of ischemic stroke | 30,36 |
| Acute lung injury (acid-induced) | Alveolar instillation of hydrochloric acid, causing sterile inflammation and injury | No data available | Leukocyte recruitment depends on presence of platelets | Pulmonary hemorrhage in the context of acute lung injury is a relevant and challenging clinical scenario | 37 |
| Acute lung injury (LPS-induced) | Alveolar LPS instillation, mimicking infectious causes of acute lung injury | Severe alveolar bleeding observed in thrombocytopenia | Leukocyte recruitment not affected by thrombocytopenia | See above | 36,38,39 |
| Dermal rpA | Model of immune complex–mediated acute inflammatory tissue injury by antigen/antibody coinjection | Severe cutaneous bleeding observed in thrombocytopenia | Platelets orchestrate leukocyte recruitment in this model | Immune complex–mediated bleeding of minor clinical relevance | 36,40 |
| Pulmonary rpA | See above; intracheal instillment | No effect reported | No effect reported | Immune complex–mediated bleeding of minor clinical relevance | 41 |
| Peritoneal rpA | See above; intraperitoneal instillment | Severe abdominal bleeding in thrombocytopenia | Reduced leukocyte recruitment in thrombocytopenia | Immune complex–mediated bleeding of minor clinical relevance | 42 |
| Tumor microvasculature | Induction of local malignoma and subsequent assessment of tumor microvasculature | Thrombocytopenia associated with hemorrhage, might be associated with higher efficiency of chemotherapy | No effect reported | Malignancy associated bleeding is a relevant clinical problem particularly in advanced tumor stages | 43,44 |
| Peritonitis (LPS-induced) | Injection of LPS into the peritoneal cavity | Inconclusive results, thrombocytopenia might result in microbleeding | Platelet depletion severely reduces leukocyte recruitment | Infection-associated peritoneal hemorrhage of minor relevance | 39,45 |
| UV-B induced dermal injury | UV-B exposure of the skin | Thrombocytopenia causes bleeding | No effect reported | Of minor clinical relevance | 46 |
| Cremasteric inflammation (LPS- or cytokine-induced) | LPS/cytokines are injected intrascrotally and the cremaster muscle is exposed for imaging/whole mount microscopy | Platelets are required to prevent microbleeds | Platelets are crucial for leukocyte recruitment in this model | Diffuse muscle bleeding is rather rare and of minor clinical importance | 38,47 |
| Inflammatory colitis | Oral administration of DSS | Platelets are required to prevent microbleeds | No data available | Major relevance of hemodynamically relevant intestinal bleeding in patients with inflammatory bowel diseases | 48 |
DSS, dextran sodium sulfate; IRI, ischemia-reperfusion injury; LPS, lipopolysaccharide; rpA, reverse-passive Arthus reaction.