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Fibrinogen Chains Intrinsic to the Brain.
Front Neurosci 2019; 13:541FN

Abstract

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 γ 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, γ immunohistochemical detection. Normal human astrocytes were grown media to confluency and stimulated with NOC-18 (100 μM), TNF-α (100 nM), ATP-γ-S (100 μM) for 24 h. 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 γ 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 h 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.

Authors+Show Affiliations

Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, United States.Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, United States.Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, United States.Division of Hematology, University of Washington School of Medicine, Seattle, WA, United States.Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, United States.Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31191233

Citation

Golanov, Eugene V., et al. "Fibrinogen Chains Intrinsic to the Brain." Frontiers in Neuroscience, vol. 13, 2019, p. 541.
Golanov EV, Sharpe MA, Regnier-Golanov AS, et al. Fibrinogen Chains Intrinsic to the Brain. Front Neurosci. 2019;13:541.
Golanov, E. V., Sharpe, M. A., Regnier-Golanov, A. S., Del Zoppo, G. J., Baskin, D. S., & Britz, G. W. (2019). Fibrinogen Chains Intrinsic to the Brain. Frontiers in Neuroscience, 13, p. 541. doi:10.3389/fnins.2019.00541.
Golanov EV, et al. Fibrinogen Chains Intrinsic to the Brain. Front Neurosci. 2019;13:541. PubMed PMID: 31191233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibrinogen Chains Intrinsic to the Brain. AU - Golanov,Eugene V, AU - Sharpe,Martyn A, AU - Regnier-Golanov,Angelique S, AU - Del Zoppo,Gregory J, AU - Baskin,David S, AU - Britz,Gavin W, Y1 - 2019/05/29/ PY - 2019/04/01/received PY - 2019/05/09/accepted PY - 2019/6/14/entrez PY - 2019/6/14/pubmed PY - 2019/6/14/medline KW - astrocytes KW - brain KW - fibrin KW - fibrinogen KW - fibrinogen chain KW - intrinsic KW - neurons KW - subarachnoid hemorrhage SP - 541 EP - 541 JF - Frontiers in neuroscience JO - Front Neurosci VL - 13 N2 - 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 γ 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, γ immunohistochemical detection. Normal human astrocytes were grown media to confluency and stimulated with NOC-18 (100 μM), TNF-α (100 nM), ATP-γ-S (100 μM) for 24 h. 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 γ 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 h 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. SN - 1662-4548 UR - https://www.unboundmedicine.com/medline/citation/31191233/Fibrinogen_Chains_Intrinsic_to_the_Brain L2 - https://dx.doi.org/10.3389/fnins.2019.00541 DB - PRIME DP - Unbound Medicine ER -