Fibrinogen Chains Intrinsic to the Brain

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.