ABSTRACT
OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS. METHODS: We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load. RESULTS: We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell-related molecules, such as CXCL13, CXCL12, IL10, and BAFF. INTERPRETATION: Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B-cell and monocyte activity are strictly correlated with cortical damage at early disease stages.
Subject(s)
Brain/pathology , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Multiple Sclerosis, Relapsing-Remitting/pathology , Adult , Blood Coagulation Factors/cerebrospinal fluid , Complement System Proteins/cerebrospinal fluid , Female , Homeostasis/physiology , Humans , Iron/metabolism , Magnetic Resonance Imaging , Male , ProteomicsABSTRACT
The authors analyze the mechanism of CSF in fibrinolytic activity in the cause of subarachnoid haemorrhage. The intrathecal administration of antifibrinolytic agents is proposed to avoid ischaemic cerebrovascular complication of systemic therapy.
Subject(s)
Blood Coagulation , Fibrinolysis , Subarachnoid Hemorrhage/cerebrospinal fluid , Animals , Blood Coagulation Factors/cerebrospinal fluid , Blood-Brain Barrier , Subarachnoid Hemorrhage/blood , Subarachnoid Hemorrhage/physiopathologySubject(s)
Blood Coagulation Factors/cerebrospinal fluid , Leukemia, Lymphoid/cerebrospinal fluid , Child , Daunorubicin/therapeutic use , Humans , Leukemia, Lymphoid/drug therapy , Leukemia, Lymphoid/radiotherapy , Methotrexate/therapeutic use , Prednisone/therapeutic use , Vincristine/therapeutic useABSTRACT
Fibrin/fibrinogen degradation products (fragments D and E) were detected in cerebrospinal fluid in 23.4% of 252 patients admitted to a neurological/neurosurgical unit. Other coagulation proteins of low molecular weight (plasminogen and factor IX) were also present but larger proteins (fibrinogen and factor V) were not. These findings are consistent with protein leakage across a blood-CSF barrier damaged by inflammatory, vascular, or neoplastic disease. Fibrin/fibrinogen degradation products in cerebrospinal fluid after subarachnoid haemorrhage may not, therefore, be a reliable index of increased fibrinolytic activity in the subarachnoid space and may be misleading when selecting patients for fibrinolytic blockade.
