phenprocoumon and Infarction--Middle-Cerebral-Artery

Secondary intracerebral hemorrhage (sICH) is a potentially serious complication of ischemic stroke, in particular under concomitant oral anticoagulation. Previous studies in murine stroke models defined a novel vascular repair function of hematogenous monocytes/macrophages (MO/MP), which proved essential for the prevention of oral anticoagulation-associated sICH. Here, we addressed the question whether hyperglycemia as a clinically relevant prohemorrhagic risk factor and peroxisome proliferator-activated receptor gamma (PPARγ) activation affect MO/MP differentiation and the risk of sICH after ischemic stroke.. Oral anticoagulation-associated sICH was induced by phenprocoumon feeding to mice undergoing transient middle cerebral artery occlusion. Hyperglycemia was induced by streptozotocin treatment. The role of PPARγ-dependent MO/MP differentiation was addressed in mice with myeloid cell-specific PPARγ-knockout (LysM-PPARγ(KO)). Pharmacological PPARγ activation via pioglitazone was tested as a treatment option.. Hyperglycemic mice and normoglycemic LysM-PPARγ(KO) mice exhibited abnormal proinflammatory skewing of their hematogenous MO/MP response and abnormal vascular remodeling in the infarct border zone, leading to an increased rate of oral anticoagulation-associated sICH. Pharmacological PPARγ activation in hyperglycemic mice corrected the inflammatory response toward an anti-inflammatory profile, stabilized neovessels in the infarct border zone, and reduced the rate of sICH. This preventive effect was dependent on the presence of macrophages, but independent from effects on blood glucose levels.. Hyperglycemia and macrophage-specific PPARγ activation exert opposing effects on MO/MP polarization in ischemic stroke lesions and, thereby, critically determine the risk of hemorrhagic infarct transformation.

Topics: Animals; Anticoagulants; Cell Polarity; Cerebral Hemorrhage; Diabetes Mellitus, Experimental; Disease Models, Animal; Gene Expression Profiling; Hyperglycemia; Hypoglycemic Agents; Infarction, Middle Cerebral Artery; Inflammation; Inflammation Mediators; Macrophages; Mice; Mice, Knockout; Monocytes; Neovascularization, Physiologic; Phenprocoumon; Pioglitazone; PPAR gamma; Risk Factors; Thiazolidinediones; Vascular Remodeling

A 55-year-old woman was referred to our hospital with signs of cerebral ischaemia i. e. dysarthria and weakness of the buccal branch of the facial nerve. Additionally the patient reported symptoms of heart failure NYHA class II. Six months earlier the patient also had visual disturbances. Magnetic resonance imaging (MRI) had shown ischaemic lesions.. A recent MRI confirmed the suspected diagnosis of ischaemia in the territory supplied by the left middle cerebral artery. The echocardiography was characterized by a reduced left ventricular ejection fraction (25 %) due to isolated ventricular non-compaction (IVNC).. The patient was treated with a combination therapy including ACE-inhibitors and diuretics. An oral anticoagulation was recommended as secondary prophylaxis. At the time of discharge the patient had no residual neurological deficits.. Isolated ventricular non-compaction is a rare type of cardiomyopathy. Possible manifestations include systemic embolic events, arrhythmias and heart failure. Echocardiography is the investigation of choice in identifying characteristic changes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Diuretics; Drug Therapy, Combination; Echocardiography; Echocardiography, Doppler, Color; Female; Heparin, Low-Molecular-Weight; Humans; Infarction, Middle Cerebral Artery; Isolated Noncompaction of the Ventricular Myocardium; Magnetic Resonance Imaging; Middle Aged; Mitral Valve Insufficiency; Phenprocoumon; Ventricular Dysfunction, Left