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Neuroprotection by recombinant thrombomodulin.

Y Taoka¹, K Okajima, M Uchiba

¹Department of Laboratory Medicine, Kumamoto University School of Medicine, Japan.

Thrombosis and Haemostasis

|April 1, 2000

Summary

Recombinant human soluble thrombomodulin (rhs-TM) reduces spinal cord injury (SCI) by inhibiting inflammation and leukocyte accumulation. Its therapeutic effects depend on protein C activation capacity, suggesting a role beyond coagulation.

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Area of Science:

Biomedical Science
Neuroscience
Hematology

Background:

Spinal cord injury (SCI) involves complex pathological processes including inflammation.
Thrombomodulin plays roles in coagulation, but its role in SCI is less understood.

Purpose of the Study:

To investigate the therapeutic potential of recombinant human soluble thrombomodulin (rhs-TM) in compression trauma-induced SCI in rats.
To determine if rhs-TM's protective effects are mediated by protein C activation.

Main Methods:

Administration of rhs-TM before or after SCI induction in a rat model.
Utilized monoclonal antibodies (MAbs) to inhibit rhs-TM's thrombin binding and protein C activation.
Assessed motor function, intramedullary hemorrhage, leukocyte accumulation, and TNF-alpha expression.

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Main Results:

rhs-TM administration significantly improved motor function and reduced hemorrhage post-SCI.
Inhibition of rhs-TM's protein C activation or thrombin binding abolished its protective effects.
rhs-TM suppressed leukocyte accumulation and TNF-alpha expression in the injured spinal cord.

Conclusions:

rhs-TM exhibits therapeutic potential against SCI, primarily through inhibiting inflammation and leukocyte infiltration.
The protein C activation pathway is crucial for rhs-TM's neuroprotective effects in SCI.
Thrombomodulin modulates both coagulation and inflammatory responses in the context of SCI.