Plasminogen activator inhibitor-1 in the pathogenesis of delayed radiation damage in rat spinal cord in vivo.
The pathophysiology of radiation-induced damage to the central nervous system (CNS) is poorly understood. Preliminary data suggest that fibrinolytic inhibitors are involved in the development of necrosis. In this study, cervical spinal cord irradiation was studied in 90 rats by measuring plasminogen activator inhibitor (PAI)-1 on Days 2, 7, 30, 60, 90, 120, 130, or 145 after irradiation. Paralysis due to radiation necrosis developed in all animals kept alive for 140 to 150 days. Assay of PAI-1 was by Western blot, enzyme-linked immunosorbent assay (ELISA), and complex formation with 125I-labeled urokinase. No PAI-1 was detected in normal spinal cord tissue or in irradiated spinal cord up to Day 90. However, PAI-1 was detected at Day 120 and was marked by elevated ELISA levels at the time of paralysis. Western blot showed detectable PAI-1 (51 kD) at Day 120 and very significant levels at the time of paralysis. Complex formation with 125I-labeled urokinase was also detected at Day 120 with similar results. Immunohistochemical studies showed that PAI-1 was highly concentrated within and immediately adjacent to zones of necrosis at 145 days and was absent in normal tissue. This study adds considerable weight to the proposal that PAI-1 is closely associated with the pathogenesis of CNS radiation necrosis.
Sawaya
R
R
Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston.
Rayford
A
A
Kono
S
S
Ang
K K
KK
Feng
Y
Y
Stephens
L C
LC
Rao
J S
JS
D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D009336:Necrosis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000737:chemistry / Q000473:pathology / Q000528:radiation effects*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D007457:Iodine Radioisotopes; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator