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The Journal of Neuroscience, February 15, 1998, 18(4):1393-1398
Activated Protein C Reduces the Severity of Compression-Induced
Spinal Cord Injury in Rats by Inhibiting Activation of Leukocytes
Yuji
Taoka1, 3,
Kenji
Okajima1,
Mitsuhiro
Uchiba1,
Kazunori
Murakami1,
Naoaki
Harada1,
Masayoshi
Johno2 and
Masakuni
Naruo3
Departments of 1 Laboratory Medicine and
2 Dermatology, Kumamoto University School of Medicine,
Kumamoto, 860, Japan, and 3 Naruo Orthopedic Hospital,
Kumamoto, 860, Japan
Activated protein C (APC), an important inhibitor of the
coagulation system, has recently been shown to prevent tissue injury by
blocking the activation of leukocytes. To determine whether APC can
also prevent post-traumatic spinal cord injury (SCI), a condition in
which leukocytes play an important role, we tested the effects of APC
on SCI induced in rats by compression trauma. Administration of APC,
either before or after the induction of SCI, markedly reduced the motor
disturbances in these animals. In contrast, neither an inactive
derivative of activated factor X (DEGR-Xa), a selective inhibitor of
thrombin generation, nor active site-blocked APC (DIP-APC) reduced the
motor disturbances. Histological examination revealed that
intramedullary hemorrhages, observed 24 hr after trauma, were
significantly reduced in the animals administered APC. The increase in
the tissue level of tumor necrosis factor- (TNF-) and the
accumulation of neutrophils in the damaged segment of the spinal cord
were significantly inhibited in the animals that had received APC, but
these were not inhibited in those administered DIP-APC or DEGR-Xa. The
induction of leukocytopenia had the same effect as APC, in that it
significantly reduced motor disturbances, tissue levels of TNF-, and
neutrophil accumulation in the animals subjected to compressive SCI.
These findings suggest that in SCI, APC reduces motor disturbances
primarily by reducing the amount of TNF- at the site of injury, thus
inhibiting neutrophil accumulation and the resultant damage to the
endothelial cells.
Key words:
activated protein C; post-traumatic spinal cord injury; leukocytes; motor disturbances; TNF-; neutrophils
Copyright © 1998 Society for Neuroscience 0270-6474/98/1841393-06$05.00/0
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