Fibrinogen and Neuroinflammation During Traumatic Brain Injury
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Fibrinogen and Neuroinflammation During Traumatic Brain Injury Nurul Sulimai 1
&
David Lominadze 1,2
Received: 25 March 2020 / Accepted: 8 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Many neurodegenerative diseases such as Alzheimer’s disease (AD), multiple sclerosis, and traumatic brain injury (TBI) are associated with systemic inflammation. Inflammation itself results in increased blood content of fibrinogen (Fg), called hyperfibrinogenemia (HFg). Fg is not only considered an acute phase protein and a marker of inflammation, but has been shown that it can cause inflammatory responses. Fibrin deposits have been associated with memory reduction in neuroinflammatory diseases such as AD and TBI. Reduction in short-term memory has been seen during the most common form of TBI, mild-tomoderate TBI. Fibrin deposits have been found in brains of patients with mild-to-moderate TBI. The vast majority of the literature emphasizes the role of fibrin-activated microglia as the mediator in the neuroinflammation pathway. However, the recent discovery that astrocytes, which constitute approximately 30% of the cells in the mammalian central nervous system, manifest different reactive states warrants further investigations in the causative role of HFg in astrocyte-mediated neuroinflammation. Our previous study showed that Fg deposited in the vasculo-astrocyte interface–activated astrocytes. However, little is known of how Fg directly affects astrocytes and neurons. In this review, we summarize studies that show the effect of Fg on different types of cells in the vasculo-neuronal unit. We will also discuss the possible mechanism of HFg-induced neuroinflammation during TBI. Keywords Astrocytes . Cortical contusion injury . Fg-PrPC complex . Neurodegeneration . Short-term memory
Introduction Fg is a soluble glycoprotein that is comprised of two sets of disulfide-bridged Aα-, Bβ-, and γ-chains. It is widely known for its central role of providing scaffolding in the coagulation cascade during hemostasis [1]. Fg is known to interact with a variety of cell receptor molecules on an array of cell types with different cellular membrane protein composition and gene expression profiles. This could be due to the nature of its molecular structure with multiple binding sites for cell receptors with different biological functions [2]. On the platelet, Fg interactions with its integrin receptors lead to platelet aggregation during coagulation events. One of its integrin receptors, GP IIb/IIIa (αIIbβ3), on the activated platelet will undergo a modification that renders it receptive to binding with ligands * David Lominadze [email protected] 1
Departments of Surgery, University of South Florida Morsani College of Medicine, MDC-4024, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA
2
Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
such as Fg or von Willebrand factor [3]. This is followed by Fg’s conversion to insoluble fibr
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