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Front. Neurosci. | doi: 10.3389/fnins.2019.00541

Fibrinogen chains intrinsic to the brain

 Eugene V. Golanov1*, Martyn A. Sharpe1, Angeliqu S. Regnier-Golanov1,  Gregory J. Del Zoppo2, David S. Baskin1 and Gavin W. Britz1
  • 1Department of Neurosurgery, Houston Methodist Hospital, United States
  • 2Division of Hematology, School of medicine, University of Washington, United States

We observed fine fibrin deposition along the paravascular spaces in naive animals, which increased dramatically following subarachnoid hemorrhage (SAH). Following SAH, fibrin deposits in the areas remote from the hemorrhage. Traditionally it is thought that fibrinogen enters subarachnoid space through damaged blood brain barrier. However, deposition of fibrin remotely from hemorrhage suggests that fibrinogen chains Aα, Bβ and  can originate in the brain. Here we demonstrate in vivo and in vitro that astroglia and neurons are capable of expression of fibrinogen chains.
SAH in mice was induced by the filament perforation of the circle of Willis. Four days after SAH animals were anesthetized, transcardially perfused and fixed. Whole brain was processed for immunofluorescent (IF) analysis of fibrin deposition on the brain surface or in brains slices processed for fibrinogen chains Aα, Bβ,  immunohistochemical detection.
Normal human astrocytes were grown media to confluency and stimulated with NOC-18 (100 μM), TNF-α (100 nM), ATP--S (100 µM) for 24 hours. Culture was fixed and washed/permeabilized with 0.1% Triton and processed for IF.
Four days following SAH fibrinogen chains Aα IF associated with glia limitans and superficial brain layers increased 3.2 and 2.5 times (p<0.05 and p<0.01) on the ventral and dorsal brain surfaces respectively; fibrinogen chains Bβ increased by 3 times (p<0.01) on the dorsal surface and fibrinogen chain  increased by 3 times (p<0.01) on the ventral surface compared to sham animals.
Human cultured astrocytes and neurons constitutively expressed all three fibrinogen chains. Their expression changed differentially when exposed for 24 hours to biologically significant stimuli: TNFα, NO or ATP. Western blot and RT-qPCR confirmed presence of the products of the appropriate molecular weight and respective mRNA.
We demonstrate for the first time that mouse and human astrocytes and neurons express fibrinogen chains suggesting potential presence of endogenous to the brain fibrinogen chains differentially changing to biologically significant stimuli. SAH is followed by increased expression of fibrinogen chains associated with glia limitans remote from the hemorrhage. We conclude that brain astrocytes and neurons are capable of production of fibrinogen chains, which may be involved in various normal and pathological processes.

Keywords: Fibrin, fibrinogen chain, Fibrinogen, astrocyte, Neuron, Immunohistochemistry, siRNA - small interfering RNA, Subarachnoid Hemorrhage, Neuroinflammation, neurodegeneration

Received: 01 Apr 2019; Accepted: 09 May 2019.

Edited by:

Johannes Boltze, Fraunhofer-Institut für Zelltherapie und Immunologie (IZI), Germany

Reviewed by:

Anatol Manaenko, University Hospital Erlangen, Germany
RICHARD F. KEEP, University of Michigan, United States  

Copyright: © 2019 Golanov, Sharpe, Regnier-Golanov, Del Zoppo, Baskin and Britz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Eugene V. Golanov, Department of Neurosurgery, Houston Methodist Hospital, Houston, United States,