There is a growing evidence that abnormalities of coagulation pathways are involved in the pathogenesis of several neurological diseases in close correlation with both neuroinflammation and neurodegeneration. Coagulation and fibrinolytic factors, together with microglia, macrophages and many different molecules including complement, cytokines, chemokines, acute phase reactants, prostaglandins, proteases, protease inhibitors, anaphylatoxins and integrins are part of innate immunity in the central nervous system (CNS). In addition, the CNS is the only site of extra-hepatic thrombin expression involved in brain development, protection, and regeneration.
The concept of thrombo-inflammation was first introduced in vascular CNS diseases when ischemic stroke was defined as a thrombo-inflammatory disorder. Despite a key role of both coagulation and venule thrombosis in multiple sclerosis (MS) pathology was suggested since its first description, the contribution of coagulation factors to MS pathogenesis has received rekindled interest only in recent years. Observation of close concordance between perivascular fibrin(ogen) deposition and occurrence of both clinical signs and microglia activation in experimental allergic encephalitis (EAE), an animal model of MS, stimulated numerous studies focused on the pro-inflammatory functions of fibrin(ogen) and on the hormone-like functions of thrombin affecting microglia and astrocytes. This is supported by the finding that disease exacerbations are characterized by a higher pro-thrombotic activity and that anticoagulant agents can induce EAE suppression or improvement.
Furthermore, there is increasing evidence that coagulation-correlated pathways affect also several CNS diseases such as amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, epilepsy, and addiction, leading to a new pathophysiological entity named neuro-coagulopathy. Finally, several studies over the last decade found a detrimental effect of thrombin in primary brain tumors enabling tumor cell seeding and metastasis and leading to increased tumor cell growth and angiogenesis.
Therefore, the study of coagulation pathways in neurological diseases would lead to a greater under-standing of their pathophysiology and a more appropriate therapeutic approach. This may meet a more general concept of immunothrombosis, i.e. formation of thrombi inside microvessels by innate immune cells and specific thrombosis-related molecules, expressing its major physiological role in immune defence rather than in haemostasis.
In this Research Topic, we welcome papers (including e.g. original research, review, perspective, commentary, opinion, hypothesis&theory articles) that add new information on involvement of both coagulation factors and innate immune components in the pathogenesis of either human neurological diseases or their animal models. We welcome contributions from scientists working in diverse disciplines (e.g. neurologists, immunologists, biologists, pathologists, neuro-oncologists, neuro-radiologists) who could contribute to this theme from different viewpoints and help compose a global framework comprising the various disorders. In order to have a more practical implication, studies on the effects of anticoagulant therapies in neurological diseases and in animal models are also welcome. While the possible relevant issues could be broad, the authors need to focus on how their studies address this topic. We hope that this Research Topic will help both researchers and clinicians to face their challenges with a more complete pathogenic approach since the role of innate immunity and of its effector coagulation factors is very relevant in both health and pathology.
There is a growing evidence that abnormalities of coagulation pathways are involved in the pathogenesis of several neurological diseases in close correlation with both neuroinflammation and neurodegeneration. Coagulation and fibrinolytic factors, together with microglia, macrophages and many different molecules including complement, cytokines, chemokines, acute phase reactants, prostaglandins, proteases, protease inhibitors, anaphylatoxins and integrins are part of innate immunity in the central nervous system (CNS). In addition, the CNS is the only site of extra-hepatic thrombin expression involved in brain development, protection, and regeneration.
The concept of thrombo-inflammation was first introduced in vascular CNS diseases when ischemic stroke was defined as a thrombo-inflammatory disorder. Despite a key role of both coagulation and venule thrombosis in multiple sclerosis (MS) pathology was suggested since its first description, the contribution of coagulation factors to MS pathogenesis has received rekindled interest only in recent years. Observation of close concordance between perivascular fibrin(ogen) deposition and occurrence of both clinical signs and microglia activation in experimental allergic encephalitis (EAE), an animal model of MS, stimulated numerous studies focused on the pro-inflammatory functions of fibrin(ogen) and on the hormone-like functions of thrombin affecting microglia and astrocytes. This is supported by the finding that disease exacerbations are characterized by a higher pro-thrombotic activity and that anticoagulant agents can induce EAE suppression or improvement.
Furthermore, there is increasing evidence that coagulation-correlated pathways affect also several CNS diseases such as amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, epilepsy, and addiction, leading to a new pathophysiological entity named neuro-coagulopathy. Finally, several studies over the last decade found a detrimental effect of thrombin in primary brain tumors enabling tumor cell seeding and metastasis and leading to increased tumor cell growth and angiogenesis.
Therefore, the study of coagulation pathways in neurological diseases would lead to a greater under-standing of their pathophysiology and a more appropriate therapeutic approach. This may meet a more general concept of immunothrombosis, i.e. formation of thrombi inside microvessels by innate immune cells and specific thrombosis-related molecules, expressing its major physiological role in immune defence rather than in haemostasis.
In this Research Topic, we welcome papers (including e.g. original research, review, perspective, commentary, opinion, hypothesis&theory articles) that add new information on involvement of both coagulation factors and innate immune components in the pathogenesis of either human neurological diseases or their animal models. We welcome contributions from scientists working in diverse disciplines (e.g. neurologists, immunologists, biologists, pathologists, neuro-oncologists, neuro-radiologists) who could contribute to this theme from different viewpoints and help compose a global framework comprising the various disorders. In order to have a more practical implication, studies on the effects of anticoagulant therapies in neurological diseases and in animal models are also welcome. While the possible relevant issues could be broad, the authors need to focus on how their studies address this topic. We hope that this Research Topic will help both researchers and clinicians to face their challenges with a more complete pathogenic approach since the role of innate immunity and of its effector coagulation factors is very relevant in both health and pathology.
