Plasminogen in cerebrospinal fluid originates from circulating blood

Area of Science:

• Neuroscience
• Biochemistry
• Immunology

Background:

• Plasminogen activation is crucial for fibrinolysis and proteolysis.
• Plasminogen plays a role in central nervous system inflammation.
• The origin of plasminogen in cerebrospinal fluid (CSF) during inflammation is debated due to the blood-CSF barrier.

Purpose of the Study:

• To investigate the origin of plasminogen in CSF during inflammation.
• To determine if plasminogen crosses the blood-CSF barrier via the choroid plexus.

Main Methods:

• Alexa Fluor 488-labeled rat plasminogen was administered to rats with lipopolysaccharide (LPS)-induced inflammation.
• Near-infrared fluorescence imaging and immunohistochemistry identified plasminogen localization.
• Western blotting and chromogenic assays measured plasminogen concentration and function.
• CSF plasminogen levels were analyzed in human patients with neurological diseases.

Main Results:

• LPS-treated rats showed increased endogenous plasminogen in CSF and urine.
• Labeled plasminogen was abundant in the choroid plexus, CSF, and urine of inflamed rats.
• Human CSF showed significantly higher plasminogen levels in Guillain-Barré syndrome patients compared to multiple sclerosis and non-inflammatory neurological disease patients.

Conclusions:

• Plasminogen is transported from blood to CSF via the choroid plexus during inflammation in rats.
• This mechanism likely explains elevated CSF plasminogen in human inflammatory neurological conditions with impaired CSF barriers.