LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats

Jakob Kaplanski; Ilia Asa; Alan A. Artru; Abed Azez; Yulia Ivashkova; Zvia Rudich; Didier Pruneau; Yoram Shapira

doi:10.1016/S0300-9572(02)00371-4

LF 16-0687 Ms, a new bradykinin B₂ receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats

Jakob Kaplanski, Ilia Asa, Alan A. Artru, Abed Azez, Yulia Ivashkova, Zvia Rudich, Didier Pruneau, Yoram Shapira

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Objective: Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B₂ receptors improves neurological status after brain injury, but the effect of B₂ antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B₂ receptor antagonist, on brain tissue PGE₂ after closed head trauma (CHT). Methods: Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE₂ (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h. Results: In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE₂ (77.7 ± 65.9 pg/mg tissue, mean ± SD) was less than in the group receiving CHT+saline (368.1 ± 186.2 pg/mg tissue) and not different than sham+saline (78.7 ± 30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%. Conclusion: We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE₂ increase in injured brain tissue.

Original language	English
Pages (from-to)	207-213
Number of pages	7
Journal	Resuscitation
Volume	56
Issue number	2
DOIs	https://doi.org/10.1016/S0300-9572(02)00371-4
State	Published - 1 Feb 2003

Keywords

Brain injury
Inflammatory response
Intracranial pressure
Neurologic dysfunction
Trauma

ASJC Scopus subject areas

Emergency Medicine
Emergency
Cardiology and Cardiovascular Medicine

Access to Document

10.1016/S0300-9572(02)00371-4

Cite this

@article{f591715a5ab5490a938303e6d62bde6b,

title = "LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats",

abstract = "Objective: Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B2 receptors improves neurological status after brain injury, but the effect of B2 antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B2 receptor antagonist, on brain tissue PGE2 after closed head trauma (CHT). Methods: Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE2 (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h. Results: In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE2 (77.7 ± 65.9 pg/mg tissue, mean ± SD) was less than in the group receiving CHT+saline (368.1 ± 186.2 pg/mg tissue) and not different than sham+saline (78.7 ± 30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%. Conclusion: We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE2 increase in injured brain tissue.",

keywords = "Brain injury, Inflammatory response, Intracranial pressure, Neurologic dysfunction, Trauma",

author = "Jakob Kaplanski and Ilia Asa and Artru, {Alan A.} and Abed Azez and Yulia Ivashkova and Zvia Rudich and Didier Pruneau and Yoram Shapira",

year = "2003",

month = feb,

day = "1",

doi = "10.1016/S0300-9572(02)00371-4",

language = "English",

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TY - JOUR

T1 - LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats

AU - Kaplanski, Jakob

AU - Asa, Ilia

AU - Artru, Alan A.

AU - Azez, Abed

AU - Ivashkova, Yulia

AU - Rudich, Zvia

AU - Pruneau, Didier

AU - Shapira, Yoram

PY - 2003/2/1

Y1 - 2003/2/1

N2 - Objective: Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B2 receptors improves neurological status after brain injury, but the effect of B2 antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B2 receptor antagonist, on brain tissue PGE2 after closed head trauma (CHT). Methods: Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE2 (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h. Results: In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE2 (77.7 ± 65.9 pg/mg tissue, mean ± SD) was less than in the group receiving CHT+saline (368.1 ± 186.2 pg/mg tissue) and not different than sham+saline (78.7 ± 30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%. Conclusion: We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE2 increase in injured brain tissue.

AB - Objective: Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B2 receptors improves neurological status after brain injury, but the effect of B2 antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B2 receptor antagonist, on brain tissue PGE2 after closed head trauma (CHT). Methods: Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE2 (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h. Results: In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE2 (77.7 ± 65.9 pg/mg tissue, mean ± SD) was less than in the group receiving CHT+saline (368.1 ± 186.2 pg/mg tissue) and not different than sham+saline (78.7 ± 30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%. Conclusion: We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE2 increase in injured brain tissue.

KW - Brain injury

KW - Inflammatory response

KW - Intracranial pressure

KW - Neurologic dysfunction

KW - Trauma

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DO - 10.1016/S0300-9572(02)00371-4

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