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Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema

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Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema. / Austinat, Madeleine; Braeuninger, Stefan; Pesquero, João B; Brede, Marc; Bader, Michael; Stoll, Guido; Renné, Thomas; Kleinschnitz, Christoph.

In: STROKE, Vol. 40, No. 1, 01.01.2009, p. 285-93.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Austinat, M, Braeuninger, S, Pesquero, JB, Brede, M, Bader, M, Stoll, G, Renné, T & Kleinschnitz, C 2009, 'Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema', STROKE, vol. 40, no. 1, pp. 285-93. https://doi.org/10.1161/STROKEAHA.108.526673

APA

Austinat, M., Braeuninger, S., Pesquero, J. B., Brede, M., Bader, M., Stoll, G., Renné, T., & Kleinschnitz, C. (2009). Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema. STROKE, 40(1), 285-93. https://doi.org/10.1161/STROKEAHA.108.526673

Vancouver

Austinat M, Braeuninger S, Pesquero JB, Brede M, Bader M, Stoll G et al. Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema. STROKE. 2009 Jan 1;40(1):285-93. https://doi.org/10.1161/STROKEAHA.108.526673

Bibtex

@article{c5a354a0574a4b8681bf19f6adcde825,
title = "Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema",
abstract = "BACKGROUND AND PURPOSE: Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators.METHODS: Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan's blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin receptor blockade, B1R and B2R inhibitors were injected.RESULTS: B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8+/-4.7 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.0001). This was accompanied by a dramatic reduction of brain edema and endothelin-1 expression, as well as less postischemic inflammation. Pharmacological blockade of B1R likewise salvaged ischemic tissue (15.0+/-9.5 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.01) in a dose-dependent manner, even when B1R inhibitor was applied 1 hour after transient middle cerebral artery occlusion. In contrast, B2R deficiency did not confer neuroprotection and had no effect on the development of tissue edema.CONCLUSIONS: These data demonstrate that blocking of B1R can diminish brain infarction and edema formation in mice and may open new avenues for acute stroke treatment in humans.",
keywords = "Animals, Bradykinin, Brain Edema, Cerebral Arteries, Cerebral Infarction, Cerebrovascular Circulation, Disease Models, Animal, Dose-Response Relationship, Drug, Down-Regulation, Encephalitis, Endothelin-1, Gene Expression, Infarction, Middle Cerebral Artery, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger, Receptor, Bradykinin B1, Receptor, Bradykinin B2",
author = "Madeleine Austinat and Stefan Braeuninger and Pesquero, {Jo{\~a}o B} and Marc Brede and Michael Bader and Guido Stoll and Thomas Renn{\'e} and Christoph Kleinschnitz",
year = "2009",
month = jan,
day = "1",
doi = "10.1161/STROKEAHA.108.526673",
language = "English",
volume = "40",
pages = "285--93",
journal = "STROKE",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

RIS

TY - JOUR

T1 - Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema

AU - Austinat, Madeleine

AU - Braeuninger, Stefan

AU - Pesquero, João B

AU - Brede, Marc

AU - Bader, Michael

AU - Stoll, Guido

AU - Renné, Thomas

AU - Kleinschnitz, Christoph

PY - 2009/1/1

Y1 - 2009/1/1

N2 - BACKGROUND AND PURPOSE: Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators.METHODS: Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan's blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin receptor blockade, B1R and B2R inhibitors were injected.RESULTS: B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8+/-4.7 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.0001). This was accompanied by a dramatic reduction of brain edema and endothelin-1 expression, as well as less postischemic inflammation. Pharmacological blockade of B1R likewise salvaged ischemic tissue (15.0+/-9.5 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.01) in a dose-dependent manner, even when B1R inhibitor was applied 1 hour after transient middle cerebral artery occlusion. In contrast, B2R deficiency did not confer neuroprotection and had no effect on the development of tissue edema.CONCLUSIONS: These data demonstrate that blocking of B1R can diminish brain infarction and edema formation in mice and may open new avenues for acute stroke treatment in humans.

AB - BACKGROUND AND PURPOSE: Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators.METHODS: Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan's blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin receptor blockade, B1R and B2R inhibitors were injected.RESULTS: B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8+/-4.7 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.0001). This was accompanied by a dramatic reduction of brain edema and endothelin-1 expression, as well as less postischemic inflammation. Pharmacological blockade of B1R likewise salvaged ischemic tissue (15.0+/-9.5 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.01) in a dose-dependent manner, even when B1R inhibitor was applied 1 hour after transient middle cerebral artery occlusion. In contrast, B2R deficiency did not confer neuroprotection and had no effect on the development of tissue edema.CONCLUSIONS: These data demonstrate that blocking of B1R can diminish brain infarction and edema formation in mice and may open new avenues for acute stroke treatment in humans.

KW - Animals

KW - Bradykinin

KW - Brain Edema

KW - Cerebral Arteries

KW - Cerebral Infarction

KW - Cerebrovascular Circulation

KW - Disease Models, Animal

KW - Dose-Response Relationship, Drug

KW - Down-Regulation

KW - Encephalitis

KW - Endothelin-1

KW - Gene Expression

KW - Infarction, Middle Cerebral Artery

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - RNA, Messenger

KW - Receptor, Bradykinin B1

KW - Receptor, Bradykinin B2

U2 - 10.1161/STROKEAHA.108.526673

DO - 10.1161/STROKEAHA.108.526673

M3 - SCORING: Journal article

C2 - 18988906

VL - 40

SP - 285

EP - 293

JO - STROKE

JF - STROKE

SN - 0039-2499

IS - 1

ER -