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Fibrinogen Chains Intrinsic to the Brain.

Eugene V Golanov1, Martyn A Sharpe1, Angelique S Regnier-Golanov1

  • 1Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, United States.

Frontiers in Neuroscience
|June 14, 2019
PubMed
Summary
This summary is machine-generated.

Brain cells like astrocytes and neurons can produce fibrinogen chains, crucial for blood clotting. This finding challenges the traditional view that fibrinogen only enters the brain from damaged blood vessels, especially after subarachnoid hemorrhage (SAH).

Keywords:
astrocytesbrainfibrinfibrinogenfibrinogen chainintrinsicneuronssubarachnoid hemorrhage

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Fibrin deposition is observed in paravascular spaces, increasing after subarachnoid hemorrhage (SAH).
  • The traditional understanding posits that fibrinogen enters the subarachnoid space solely through a damaged blood-brain barrier.

Purpose of the Study:

  • To investigate the potential for endogenous production of fibrinogen chains (Aα, Bβ, and γ) within the brain.
  • To explore the role of astroglia and neurons in expressing fibrinogen chains.
  • To examine changes in fibrinogen chain expression following SAH.

Main Methods:

  • Subarachnoid hemorrhage (SAH) was induced in mice via filament perforation of the circle of Willis.
  • Immunofluorescence (IF) and immunohistochemistry were used to detect fibrin deposition and fibrinogen chains in brain slices.
  • Human astrocytes and neurons were cultured and stimulated with NOC-18, TNF-α, and ATP-γ-S, followed by IF analysis. Western blot and RT-qPCR confirmed gene and protein expression.

Main Results:

  • Following SAH, increased expression of fibrinogen chains Aα, Bβ, and γ was observed in brain layers remote from the hemorrhage.
  • Cultured human astrocytes and neurons constitutively expressed all three fibrinogen chains.
  • Stimulation with TNFα, NO, or ATP differentially altered fibrinogen chain expression in cultured brain cells.

Conclusions:

  • Astrocytes and neurons are capable of expressing fibrinogen chains, suggesting an endogenous source of fibrinogen within the brain.
  • Fibrinogen chain expression in the brain is dynamic and responds to biologically significant stimuli.
  • Endogenous fibrinogen produced by brain cells may play a role in both normal physiological and pathological processes, including SAH.