Effects of LF 16-0687 Ms, a bradykinin B2 receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia

Zausinger, Stefan; Lumenta, David B.; Pruneau, Didier; Schmid-Elsaesser, Robert; Plesnila, Nikolaus; Baethmann, A.

doi:10.1016/s0006-8993(02)03053-6

Cited by 68 publications

(49 citation statements)

References 54 publications

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“…Numerous studies did not find a detrimental effect of B2R deficiency or blockade on stroke outcome. 12,54,55 Infarct size in WT mice after 90 minutes of MCAO was surprisingly small in the study by Xia et al, 53 whereas the B2R KO mice had developed infarcts that were the size that one would usually expect in WT mice after 90 minutes of tMCAO. We and others 27,28,55,56 could demonstrate that 60 minutes of occlusion of the MCA already causes infarct volumes between 50 and 80 mm 3 at day 1 after MCAO, eg, in C57BL/6, SV129, or Swiss mice.…”

Section: Discussionmentioning

confidence: 97%

Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema

Austinat

Braeuninger²,

Pesquero³

et al. 2009

Stroke

137

119

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Section: Discussionmentioning

confidence: 97%

Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema

Austinat

Braeuninger²,

Pesquero³

et al. 2009

Stroke

137

119

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“…However, increasing evidence indicates that the kallikrein-kinin system mediates neuroprotection in ischemic brain injury Chao, 2005, 2006;Zausinger et al, 2002). This type of neuroprotection may be a direct effect of the B2 receptor on neuronal survival (Groger et al, 2005), or of direct activation of the kinin B2 receptor without kinin formation (Chao et al, 2008), or the suppression of mitochondrial pore opening and reducing oxidative stress, or the activation of Akt-mediated signaling pathways (Chao and Chao, 2005).…”

Section: Discussionmentioning

confidence: 99%

Human Urinary Kallidinogenase Suppresses Cerebral Inflammation in Experimental Stroke and Downregulates Nuclear Factor-κB

Chen

Huang

Niu

et al. 2010

J Cereb Blood Flow Metab

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The purpose of this study is to investigate the possible mechanism and the neuroprotective effect of human urinary kallidinogenase (HUK) in cerebral ischemia. The mouse middle cerebral artery occlusion (MCAO) model was used. Mice were treated with HUK (20 PNAU/g per day, intravenous) or saline as control, from the beginning of reperfusion to 72 h. Neurological deficits, infarct size, and BWC were measured at 6, 24, 48, and 72 h after MCAO, respectively. Pathological changes of brain were observed by TUNEL assay. Inflammatory factors were measured by real-time PCR and western blotting. Activation of MAPKs, Akt, and nuclear factor-jB (NF-jB) was detected by western blotting. Our results indicated that HUK significantly improved neurofunction, decreased infarct size, and suppressed edema, as well as inflammatory mediators as compared with the vehicle group. Furthermore, HUK inhibited the NF-jB pathway and activated the MAPK/ERK pathway in this neuroprotection.

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“…In experimental stroke, several studies using bradykinin B 2 receptor antagonists showed reduced brain edema and infarct formation after transient and permanent occlusion of the middle cerebral artery (MCA) in mouse and rat (Relton et al, 1996(Relton et al, , 1997Zausinger et al, 2002;Ding-Zhou et al, 2003). Despite these encouraging results, the kallikrein-kinin system has not been studied further in focal cerebral ischemia.…”

Section: Introductionmentioning

confidence: 99%

Release of Bradykinin and Expression of Kinin B₂Receptors in the Brain: Role for Cell Death and Brain Edema Formation After Focal Cerebral Ischemia in Mice

Gröger¹,

Lebesgue

Pruneau

et al. 2005

J Cereb Blood Flow Metab

127

112

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Pharmacological studies using bradykinin B 2 receptor antagonists suggest that bradykinin, an early mediator of inflammation and the main metabolite of the kallikrein-kinin system, is involved in secondary brain damage after cerebral ischemia. However, the time-course of bradykinin production and kinin receptor expression as well as the conclusive role of bradykinin B 2 receptors for brain damage after experimental stroke have not been elucidated so far. C57/Bl6 mice were subjected to 45 mins of middle cerebral artery occlusion (MCAO) and 2, 4, 8, 24, and 48 h later brains were removed for the analysis of tissue bradykinin concentration and kinin B 2 receptor mRNA and protein expression. Brain edema, infarct volume, functional outcome, and long-term survival were assessed in WT and B 2 À/À mice 24 h or 7 days after MCAO. Tissue bradykinin was maximally increased 12 h after ischemia (three-fold), while kinin B 2 receptor mRNA upregulation peaked 24 to 48 h after MCAO (10-to 12-fold versus naïve brain tissue). Immunohistochemistry revealed that kinin B 2 receptors were constitutively and widely expressed in mouse brain, were upregulated 2 h after ischemia in cells showing signs of ischemic damage, and remained upregulated in the penumbra up to 24 h after ischemia. B 2 À/À mice had improved motor function (Po0.05), smaller infarct volumes (À38%; Po0.01), developed less brain edema (À87%; Po0.05), and survived longer (Po0.01) as compared with wild-type controls. The current results show that bradykinin is produced in the brain, kinin B 2 receptors are upregulated on dying cells, and B 2 receptors are involved in cell death and brain edema formation after experimental stroke.

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Effects of LF 16-0687 Ms, a bradykinin B2 receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia

Cited by 68 publications

References 54 publications

Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema

Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema

Human Urinary Kallidinogenase Suppresses Cerebral Inflammation in Experimental Stroke and Downregulates Nuclear Factor-κB

Release of Bradykinin and Expression of Kinin B₂Receptors in the Brain: Role for Cell Death and Brain Edema Formation After Focal Cerebral Ischemia in Mice

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Effects of LF 16-0687 Ms, a bradykinin B2 receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia

Cited by 68 publications

References 54 publications

Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema

Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema

Human Urinary Kallidinogenase Suppresses Cerebral Inflammation in Experimental Stroke and Downregulates Nuclear Factor-κB

Release of Bradykinin and Expression of Kinin B2Receptors in the Brain: Role for Cell Death and Brain Edema Formation After Focal Cerebral Ischemia in Mice

Contact Info

Product

Resources

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Release of Bradykinin and Expression of Kinin B₂Receptors in the Brain: Role for Cell Death and Brain Edema Formation After Focal Cerebral Ischemia in Mice