LF 16-0687Ms, a new bradykinin b2 receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin e2 release in a rat model of closed head trauma combined with ethanol intoxication

Ilia Asa; Yulia Ivashkova; Alan A. Artru; Matityahu Lifshitz; Gavrilov Lifshitz; Abed N. Azab; Vladimir Kapuler; Andrei Alouchin; Maxim Rachinsky; Didier Pruneau; Yoram Shapira; Jacob Kaplanski

doi:10.1097/01.TA.0000046700.45106.4B

LF 16-0687Ms, a new bradykinin b₂ receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin e₂ release in a rat model of closed head trauma combined with ethanol intoxication

Ilia Asa, Yulia Ivashkova, Alan A. Artru, Matityahu Lifshitz, Gavrilov Lifshitz, Abed N. Azab, Vladimir Kapuler, Andrei Alouchin, Maxim Rachinsky, Didier Pruneau, Yoram Shapira, Jacob Kaplanski

Basic Sciences Divisions

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

4 Scopus citations

Abstract

Background: LF 16-0687 Ms previously wasreported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E₂ (PGE₂) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration. Methods: Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline. Results: After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline orethanol. PGE₂ release decreased with ethanol (147 ± 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 ± 194 pg/mg tissue).Conclusion Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE₂ release. In intoxicated patients, bradykinin antagonist therapy mayimprove post-CHT outcome without altering PGE₂ release.

Original language	English
Pages (from-to)	881-887
Number of pages	7
Journal	Journal of Trauma
Volume	52
Issue number	5
DOIs	https://doi.org/10.1097/01.TA.0000046700.45106.4B
State	Published - 1 Jan 2003

Keywords

Bradykinin Bantagonist
Cerebral edema
Ethanol
Head injury
Neurologic outcome
Prostaglandin
Rat

ASJC Scopus subject areas

Surgery
Critical Care and Intensive Care Medicine

Access to Document

10.1097/01.TA.0000046700.45106.4B

Cite this

Asa, I., Ivashkova, Y., Artru, A. A., Lifshitz, M., Lifshitz, G., Azab, A. N., Kapuler, V., Alouchin, A., Rachinsky, M., Pruneau, D., Shapira, Y., & Kaplanski, J. (2003). LF 16-0687Ms, a new bradykinin b₂ receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin e₂ release in a rat model of closed head trauma combined with ethanol intoxication. Journal of Trauma, 52(5), 881-887. https://doi.org/10.1097/01.TA.0000046700.45106.4B

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title = "LF 16-0687Ms, a new bradykinin b2 receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin e2 release in a rat model of closed head trauma combined with ethanol intoxication",

abstract = "Background: LF 16-0687 Ms previously wasreported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E2 (PGE2) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration. Methods: Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline. Results: After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline orethanol. PGE2 release decreased with ethanol (147 ± 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 ± 194 pg/mg tissue).Conclusion Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE2 release. In intoxicated patients, bradykinin antagonist therapy mayimprove post-CHT outcome without altering PGE2 release.",

keywords = "Bradykinin Bantagonist, Cerebral edema, Ethanol, Head injury, Neurologic outcome, Prostaglandin, Rat",

author = "Ilia Asa and Yulia Ivashkova and Artru, {Alan A.} and Matityahu Lifshitz and Gavrilov Lifshitz and Azab, {Abed N.} and Vladimir Kapuler and Andrei Alouchin and Maxim Rachinsky and Didier Pruneau and Yoram Shapira and Jacob Kaplanski",

year = "2003",

month = jan,

day = "1",

doi = "10.1097/01.TA.0000046700.45106.4B",

language = "English",

volume = "52",

pages = "881--887",

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Asa, I, Ivashkova, Y, Artru, AA, Lifshitz, M, Lifshitz, G, Azab, AN, Kapuler, V, Alouchin, A, Rachinsky, M, Pruneau, D, Shapira, Y & Kaplanski, J 2003, 'LF 16-0687Ms, a new bradykinin b₂ receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin e₂ release in a rat model of closed head trauma combined with ethanol intoxication', Journal of Trauma, vol. 52, no. 5, pp. 881-887. https://doi.org/10.1097/01.TA.0000046700.45106.4B

LF 16-0687Ms, a new bradykinin b₂ receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin e₂ release in a rat model of closed head trauma combined with ethanol intoxication. / Asa, Ilia; Ivashkova, Yulia; Artru, Alan A. et al.
In: Journal of Trauma, Vol. 52, No. 5, 01.01.2003, p. 881-887.

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

TY - JOUR

T1 - LF 16-0687Ms, a new bradykinin b2 receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin e2 release in a rat model of closed head trauma combined with ethanol intoxication

AU - Asa, Ilia

AU - Ivashkova, Yulia

AU - Artru, Alan A.

AU - Lifshitz, Matityahu

AU - Lifshitz, Gavrilov

AU - Azab, Abed N.

AU - Kapuler, Vladimir

AU - Alouchin, Andrei

AU - Rachinsky, Maxim

AU - Pruneau, Didier

AU - Shapira, Yoram

AU - Kaplanski, Jacob

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Background: LF 16-0687 Ms previously wasreported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E2 (PGE2) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration. Methods: Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline. Results: After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline orethanol. PGE2 release decreased with ethanol (147 ± 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 ± 194 pg/mg tissue).Conclusion Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE2 release. In intoxicated patients, bradykinin antagonist therapy mayimprove post-CHT outcome without altering PGE2 release.

AB - Background: LF 16-0687 Ms previously wasreported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E2 (PGE2) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration. Methods: Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline. Results: After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline orethanol. PGE2 release decreased with ethanol (147 ± 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 ± 194 pg/mg tissue).Conclusion Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE2 release. In intoxicated patients, bradykinin antagonist therapy mayimprove post-CHT outcome without altering PGE2 release.

KW - Bradykinin Bantagonist

KW - Cerebral edema

KW - Ethanol

KW - Head injury

KW - Neurologic outcome

KW - Prostaglandin

KW - Rat

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U2 - 10.1097/01.TA.0000046700.45106.4B

DO - 10.1097/01.TA.0000046700.45106.4B

M3 - Article

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SN - 0022-5282

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EP - 887

JO - Journal of Trauma

JF - Journal of Trauma

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