fibrin and Encephalitis

Topics: Abciximab; Allergy and Immunology; Animals; Blood-Brain Barrier; Bloodless Medical and Surgical Procedures; Encephalitis; Fibrin; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Immunity, Innate; Immunotherapy; Mice; Multiple Sclerosis; Tumor Necrosis Factor-alpha

Intracerebral hemorrhage (ICH) is a severe type of stroke without effective treatment. The coagulation cascade is activated after blood flows into the brain parenchyma. The conversion of fibrinogen to fibrin is an essential step of coagulation processes, but its influences on neuroinflammation and long-term outcome after ICH have not been adequately studied. Hirudin binds to thrombin and inhibits the conversion of fibrinogen to fibrin. We therefore investigated the impact of hirudin treatment on brain inflammation and long-term outcome of ICH in mice.. Fibrinogen levels were measured in plasma samples from patients with ICH. In mice subjected to collagenase injection, fibrinogen levels were measured in the plasma and brain. The impact of hirudin on neuroinflammation and long-term neurological outcome was determined in ICH mice.. Circulating fibrinogen level was increased in patients with ICH at day 1 and day 4 after onset. In ICH mice, fibrinogen levels in the blood and brain were increased at day 7. Delayed daily administration of hirudin from day 7 to day 28 significantly improved long-term outcome in ICH mice. Hirudin treatment reduced leukocyte accumulation in the brain and shifted microglia toward an anti-inflammatory phenotype. In addition, depletion of microglia in ICH mice diminished the benefit of hirudin in ICH mice.. These results suggest that inhibition of fibrin formation alleviates brain inflammation and improves long-term outcome after ICH.

Topics: Animals; Brain; Cerebral Hemorrhage; Encephalitis; Female; Fibrin; Fibrinogen; Hirudin Therapy; Hirudins; Humans; Male; Mice, Inbred C57BL

It is known that both platelets and coagulation strongly influence infarct progression after ischemic stroke, but the mechanisms and their interplay are unknown. Our aim was to assess the contribution of the procoagulant platelet surface, and thus platelet-driven thrombin generation, to the progression of thromboinflammation in the ischemic brain.. We present the characterization of a novel platelet and megakaryocyte-specific TMEM16F (anoctamin 6) knockout mouse. Reflecting Scott syndrome, platelets from the knockout mouse had a significant reduction in procoagulant characteristics that altered thrombin and fibrin generation kinetics. In addition, knockout mice showed significant defects in hemostasis and arterial thrombus formation. However, infarct volumes in a model of ischemic stroke were comparable with wild-type mice.. Platelet TMEM16F activity contributes significantly to hemostasis and thrombosis but not cerebral thromboinflammation. These results highlight another key difference between the roles of platelets and coagulation in these processes.

Topics: Animals; Anoctamins; Blood Coagulation; Blood Platelets; Carotid Artery Diseases; Disease Models, Animal; Encephalitis; Fibrin; Hemostasis; Infarction, Middle Cerebral Artery; Kinetics; Megakaryocytes; Mice, Inbred C57BL; Mice, Knockout; Phosphatidylserines; Phospholipid Transfer Proteins; Platelet Activation; Signal Transduction; Thrombin; Thrombosis

Cerebral vascular lesions of 26 cases in systemic lupus erythematosus during a period from 1963 to 1978 were examined histologically and the following conclusions were made: 1. The prominent vascular changes of the brain were thrombosis, fibrinoid degeneration, endothelial swelling and proliferation, arteriolosclerosis, and perivascular infiltration of inflammatory cells. 2. From clinico-pathological viewpoints, thrombosis seemed to play an important role in the development of neurological signs. In five cases, characteristic granular or homogeneous thrombi were observed in the small blood vessels including venule. Infarct without proved vascular obstruction but probably due to thrombosis was seen in four cases. The true character of the granular thrombi was not determined, either electronmicroscopically or immunohistochemically. These suggested the presence of a tendency for in situ formation of thrombus. 3. Fibrinoid degeneration seen in four cases mainly affected arterile of less than 50 micrometer in diameter in the cerebral cortex, basal ganglia, and brain stem. This change of arteriole did not play a significant role in neurological signs. 4. Endothelial swelling and proliferation of the small blood vessels were prominent in the cases with thrombosis and fibrinoid degeneration. 5. Perivascular infiltration of the inflammatory cells was observed in about one-half of the cases but its significance was not clear.

Topics: Adolescent; Adult; Blood Vessels; Brain; Brain Diseases; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Child; Encephalitis; Endothelium; Female; Fibrin; Humans; Intracranial Arteriosclerosis; Intracranial Embolism and Thrombosis; Lupus Erythematosus, Systemic; Male; Middle Aged

Paired cerebrospinal fluid (CSF) and serum samples collected from 81 of 241 patients admitted to a district psychiatric hospital during a six month period were assayed for fibrin/fibrinogen degradation products (FDP) using a haemagglutination inhibition technique. FDP were found in all serum samples. Fifteen patients (18·5%) had FDP in the CSF (range 0·7-3·75 μg/ml.) and of these 13 (87%) had associated CSF protein abnormalities and 9 (60%) were hypertensive. Mean serum FDP values were the same (4·4 μg/ml.) in patients with and without FDP in the CSF. Three patients had raised serum FDP concentrations but no FDP in the CSF. The evidence suggests that the presence of FDP in CSF indicates recent central nervous system damage. In this series the most common cause was vascular disease.

Topics: Adult; Aged; Blood Pressure; Brain Diseases; Brain Neoplasms; Cerebrospinal Fluid Proteins; Cerebrovascular Disorders; Encephalitis; Female; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Intracranial Arteriosclerosis; Male; Middle Aged

Topics: Abortion, Septic; Adolescent; Adult; Anticoagulants; Antithrombins; Blood; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Disseminated Intravascular Coagulation; Encephalitis; Encephalitis Viruses; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Liver; Male; Necrosis; Pituitary Gland; Pregnancy; Prostatic Neoplasms; Prothrombin; Sepsis; Shock, Septic; Spleen; Streptokinase

Topics: Central Nervous System Diseases; Cerebral Hemorrhage; Child; Encephalitis; Fibrin; Hematoma; Hematoma, Subdural; Humans; Hydrocephalus; Intracranial Embolism; Intracranial Embolism and Thrombosis; Meningitis; Pathology