Bradykinin antagonist decreases early disruption of the blood-spinal cord barrier after spinal cord injury in mice.
Bradykinin is one of the key molecules involved in the disruption of the blood-brain barrier and blood-spinal cord barrier occurring after spinal cord injury (SCI). Previously we have shown a biphasic opening of the blood-spinal cord barrier as well as increased transport of tumor necrosis factor-alpha (TNFalpha) after SCI by compression of the lumbar spinal cord in mice. To evaluate the role of bradykinin in the two phases of blood-spinal cord barrier disruption, we pretreated mice with a potent bradykinin antagonist, the decapeptide B9430, before SCI. Our results show that B9430 decreased the general blood-spinal cord barrier disruption occurring immediately after SCI but failed to affect the delayed opening of the blood-spinal cord barrier observed 72 h after SCI. By contrast, the entry of TNFalpha after SCI was not affected by B9430 treatment. We conclude that bradykinin is involved in the early phase of blood-spinal cord barrier disruption, with B9430 non-selectively blocking this early disruption without affecting the selective transport system for TNFalpha. This indicates the therapeutic potential of bradykinin antagonists in ameliorating tissue damage induced by SCI.
Pan
W
W
VA Medical Center and Department of Medicine, Tulane University School of Medicine, 1601 Perdido Street, New Orleans, LA 70112, USA. wpan@tulane.edu
Kastin
A J
AJ
Gera
L
L
Stewart
J M
JM
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C121351:B 9430; D007457:Iodine Radioisotopes; D013668:Technetium Tc 99m Aggregated Albumin; D014409:Tumor Necrosis Factor-alpha; D001920:Bradykinin