Bradykinin Activates the Bradykinin B2 Receptor to Ameliorate Neuronal Injury in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury

Abstract

Bradykinin and bradykinin B2 receptors (B2R) play important roles in both the peripheral and central nervous systems. The aim of this study was to explore the changes of bradykinin and B2R in spinal cord ischemic injury (SCII) and whether bradykinin treatment would improve the neurologic function of SCII rats. The rats were divided into the sham group, the SCII group, and three doses of bradykinin (50, 100, 150 μg/kg) groups. The neurologic function was assessed by the Basso, Beattie, and Bresnahan (BBB) score at −1, 1, 3, 5, and 7 days postsurgery. Bradykinin concentration in serum and IL-6, TNF-α, and MCP-1 levels in the spinal cord were detected by ELISA. The mRNA expressions of B2R, IL-6, TNF-α, MCP-1, COX-2, and iNOS in the spinal cord were determined by RT-PCR. The protein expressions of B2R, COX-2, iNOS, p65, and p-p65 were detected by Western blot. Immunohistochemical staining was used to examine B2R expression in the L4−6 segments of the spinal cord. Bradykinin levels in serum and B2R expression in the spinal cord were downregulated in SCII rats. Bradykinin treatment significantly improved the hind limb motor function of SCII rats and increased B2R expression, inhibiting COX-2, iNOS, and p-p65 expression in the spinal cord of SCII rats together with a decrease of the inflammatory mediators of IL-6, TNF-α, and MCP-1 levels. Bradykinin administration activated B2R in the spinal cord of SCII rats, which may improve hind limb locomotor recovery by regulating the NF-κB signaling pathway to inhibit the inflammatory response. These findings may provide a theoretical basis for the clinical application of bradykinin in SCII.

Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium

“…Bradykinin is a peptide released in these injuries, that mediates inflammatory response, vasodilatation and damage to the blood-brain barrier [ 55 ]. Therefore, bradykinin, through its receptor B1 and B2, has been linked to mediate the deleterious effects of ischemia–reperfusion [ 44 , 53 , 56 ]. Interestingly, NOSC has shown protective effects against ischemia–reperfusion injury by blocking bradykinin receptors [ 44 , 53 ].…”

Diallyl trisulfide improves spinal cord ischemia–reperfusion injury damage by activating AMPK to stabilize mitochondrial function

“…The observer gently tapped the basin wall to make the rats crawl, and scored them according to their walking and coordination. The assessment included limb movement, extent of abdomen drag, trunk position and stability, claw position and placement, tail position, and gait, with a score of 0 indicating complete loss of motor function and a score of 21 indicating normal motor ability [ 15 , 16 ].…”

Development of a multigram synthesis of the bradykinin receptor 2 agonist FR‐190997 and analogs thereof

“…BK action has been shown to be implicated in inflammation, nociception, autoimmunity, vasculopathy, viral infections, diabetes, CNS disorders, and many cancers. [ 3–16 ] In the context of cancer, biochemical research had established that long‐term stimulation of B1R and B2R induce growth and invasion of cancer cells which led to an intense interest in developing initially peptidic and more recently nonpeptidic B2R (and B1R) antagonists as antiproliferative agents. [ 17–23 ] Intrigued by seemingly contradictory reports supporting that peptidic B1R agonists also provide antiproliferative benefits, [ 24–26 ] we decided to test a B2R agonist anticipating that the more widespread expression of the B2 receptor could precipitate a more profound antiproliferative effect.…”