Bradykinin antagonist decreases early disruption of the blood-spinal cord barrier after spinal cord injury in mice

Neurosci Lett. 2001 Jul 6;307(1):25-8. doi: 10.1016/s0304-3940(01)01904-8.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / physiology
  • Bradykinin / analogs & derivatives
  • Bradykinin / antagonists & inhibitors*
  • Bradykinin / metabolism
  • Bradykinin / pharmacology*
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology
  • Iodine Radioisotopes / pharmacokinetics
  • Male
  • Mice
  • Mice, Inbred ICR
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology
  • Technetium Tc 99m Aggregated Albumin / pharmacokinetics
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*


  • B 9430
  • Iodine Radioisotopes
  • Technetium Tc 99m Aggregated Albumin
  • Tumor Necrosis Factor-alpha
  • Bradykinin