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Erschienen in: Translational Stroke Research 2/2011

01.06.2011

Acute Treatment with Candesartan Reduces Early Injury After Permanent Middle Cerebral Artery Occlusion

verfasst von: Weihua Guan, Anna Kozak, Azza B. El-Remessy, Maribeth H. Johnson, Bindu A. Pillai, Susan C. Fagan

Erschienen in: Translational Stroke Research | Ausgabe 2/2011

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Abstract

We have shown that reduction of blood pressure (BP) immediately after the onset of reperfusion reduced neurovascular damage and improved functional outcome after experimental cerebral ischemia and candesartan is particularly effective in improving long-term functional outcome. In this study, we sought to determine if early BP lowering with candesartan, in the presence of an occluded cerebral artery, will reduce injury and improve outcome after experimental stroke. Male Wistar rats underwent 24 h or 7 days of middle cerebral artery occlusion (MCAO). A single dose of 1 mg/kg candesartan was administered intravenously at 3 h after MCAO. Animals received neurobehavioral testing at 3 h, 24 h, and 7 days, and blood pressure was measured by telemetry. Animals had brain tissue collected for infarct size (24 h and 7 days), hemoglobin content, matrix metalloproteinase (MMP) activity, and vascular endothelial growth factor (VEGF) expression (24 h only). Candesartan significantly decreased blood pressure, infarct size (−20%; p = 0.021), hemoglobin excess (−50%; p = 0.0013), and edema (−35%; p = 0.0005) at 24 h after MCAO. This resulted in a reduced cerebral perfusion deficit (p = 0.034) in the ischemic hemisphere compared with saline and significantly improved Bederson scores and paw grasp. MMP-2, MMP-9, and VEGF were significantly increased by MCAO, but there were no differences between candesartan- and saline-treated animals. There were no significant differences in behavioral outcome at day 7. BP lowering with candesartan reduces early brain injury after experimental stroke even when the artery remains occluded. The early benefits were not sustained at 7 days, as seen in reperfused animals, however. The neuroprotection and neurorestorative properties of candesartan may occur by separate distinct mechanisms.
Literatur
1.
Zurück zum Zitat Sare GM, Geeganage C, Bath PM. High blood pressure in acute ischaemic stroke—broadening therapeutic horizons. Cerebrovasc Dis. 2009;27 Suppl 1:156–61.PubMedCrossRef Sare GM, Geeganage C, Bath PM. High blood pressure in acute ischaemic stroke—broadening therapeutic horizons. Cerebrovasc Dis. 2009;27 Suppl 1:156–61.PubMedCrossRef
2.
Zurück zum Zitat Sare GM, Ali M, Shuaib A, Bath PM, VISTA Collaboration. Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA collaboration. Stroke. 2009;40:2098–103.PubMedCrossRef Sare GM, Ali M, Shuaib A, Bath PM, VISTA Collaboration. Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA collaboration. Stroke. 2009;40:2098–103.PubMedCrossRef
3.
Zurück zum Zitat Kozak W, Kozak A, Johnson MH, Elewa HF, Fagan SC. Vascular protection with candesartan after experimental acute stroke in hypertensive rats: a dose–response study. J Pharmacol Exp Ther. 2008;326:773–82.PubMedCrossRef Kozak W, Kozak A, Johnson MH, Elewa HF, Fagan SC. Vascular protection with candesartan after experimental acute stroke in hypertensive rats: a dose–response study. J Pharmacol Exp Ther. 2008;326:773–82.PubMedCrossRef
4.
Zurück zum Zitat Elewa HF, Kozak A, Johnson MH, Ergul A, Fagan SC. Blood pressure lowering after experimental cerebral ischemia provides neurovascular protection. J Hypertens. 2007;25:855–9.PubMedCrossRef Elewa HF, Kozak A, Johnson MH, Ergul A, Fagan SC. Blood pressure lowering after experimental cerebral ischemia provides neurovascular protection. J Hypertens. 2007;25:855–9.PubMedCrossRef
5.
Zurück zum Zitat Fagan SC, Kozak A, Hill WD, Pollock DM, Xu L, Johnson MH, et al. Hypertension after experimental cerebral ischemia: candesartan provides neurovascular protection. J Hypertens. 2006;24:535–9.PubMedCrossRef Fagan SC, Kozak A, Hill WD, Pollock DM, Xu L, Johnson MH, et al. Hypertension after experimental cerebral ischemia: candesartan provides neurovascular protection. J Hypertens. 2006;24:535–9.PubMedCrossRef
6.
Zurück zum Zitat Kozak A, Ergul A, El-Remessy AB, Johnson MH, Machado LS, Elewa HF, et al. Candesartan augments ischemia-induced proangiogenic state and results in sustained improvement after stroke. Stroke. 2009;40:1870–6.PubMedCrossRef Kozak A, Ergul A, El-Remessy AB, Johnson MH, Machado LS, Elewa HF, et al. Candesartan augments ischemia-induced proangiogenic state and results in sustained improvement after stroke. Stroke. 2009;40:1870–6.PubMedCrossRef
7.
Zurück zum Zitat Engelhorn T, Goerike S, Doerfler A, Okorn C, Forsting M, Heusch G, et al. The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats. J Cereb Blood Flow Metab. 2004;24:467–74.PubMedCrossRef Engelhorn T, Goerike S, Doerfler A, Okorn C, Forsting M, Heusch G, et al. The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats. J Cereb Blood Flow Metab. 2004;24:467–74.PubMedCrossRef
8.
Zurück zum Zitat Saqqur M, Tsivgoulis G, Molina CA, Demchuk AM, Siddiqui M, Alvarez-Sabín J, et al. CLOTBUST Investigators. Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: a multicenter study. Neurology. 2008;71:1304–12.PubMedCrossRef Saqqur M, Tsivgoulis G, Molina CA, Demchuk AM, Siddiqui M, Alvarez-Sabín J, et al. CLOTBUST Investigators. Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: a multicenter study. Neurology. 2008;71:1304–12.PubMedCrossRef
9.
Zurück zum Zitat Zea Longa E, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy. Stroke. 1989;20:84–91. Zea Longa E, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy. Stroke. 1989;20:84–91.
10.
Zurück zum Zitat Hilali HM, Simpkins AN, Hill WD, Waller JL, Knight RA, Fagan SC. Single slice method for quantification of hemorrhagic transformation using Direct ELISA. Neurol Res. 2004;26:93–8.PubMedCrossRef Hilali HM, Simpkins AN, Hill WD, Waller JL, Knight RA, Fagan SC. Single slice method for quantification of hemorrhagic transformation using Direct ELISA. Neurol Res. 2004;26:93–8.PubMedCrossRef
11.
Zurück zum Zitat Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke. 1986;17:1304–8.PubMed Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke. 1986;17:1304–8.PubMed
12.
Zurück zum Zitat Machado LS, Kozak A, Ergul A, Hess DC, Borlongan CV, Fagan SC. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci. 2006;7:56–62.PubMedCrossRef Machado LS, Kozak A, Ergul A, Hess DC, Borlongan CV, Fagan SC. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci. 2006;7:56–62.PubMedCrossRef
13.
Zurück zum Zitat Abdelsaid MA, Pillai BA, Matragoon S, Prakash R, Al-Shabrawey M, El-Remessy AB. Early intervention of tyrosine nitration prevents vaso-obliteration and neovascularization in ischemic retinopathy. J Pharmacol Exp Ther. 2010;332:125–34.PubMedCrossRef Abdelsaid MA, Pillai BA, Matragoon S, Prakash R, Al-Shabrawey M, El-Remessy AB. Early intervention of tyrosine nitration prevents vaso-obliteration and neovascularization in ischemic retinopathy. J Pharmacol Exp Ther. 2010;332:125–34.PubMedCrossRef
14.
Zurück zum Zitat Borlongan CV, Sanberg PR. Elevated body swing test: a new behavioral parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism. J Neurosci. 1995;15:5372–8.PubMed Borlongan CV, Sanberg PR. Elevated body swing test: a new behavioral parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism. J Neurosci. 1995;15:5372–8.PubMed
15.
Zurück zum Zitat Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986;17:472–6.PubMed Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986;17:472–6.PubMed
16.
Zurück zum Zitat Meyer JS, Shimazu K, Fukuuchi Y, Ohuchi T, Okamoto S, Koto A, et al. Impaired neurogenic cerebrovascular control and dysautoregulation after stroke. Stroke. 1973;14:169–86. Meyer JS, Shimazu K, Fukuuchi Y, Ohuchi T, Okamoto S, Koto A, et al. Impaired neurogenic cerebrovascular control and dysautoregulation after stroke. Stroke. 1973;14:169–86.
17.
Zurück zum Zitat Guo S, Kim WJ, Lok J, Lee SR, Besancon E, Luo BH, et al. Neuroprotection via matrix–trophic coupling between cerebral endothelial cells and neurons. PNAS. 2008;105(21):7582–7.PubMedCrossRef Guo S, Kim WJ, Lok J, Lee SR, Besancon E, Luo BH, et al. Neuroprotection via matrix–trophic coupling between cerebral endothelial cells and neurons. PNAS. 2008;105(21):7582–7.PubMedCrossRef
18.
Zurück zum Zitat Hamai M, Iwai M, Ide A, Tomochika H, Tomono Y, Mogi M, et al. Comparison of inhibitory action of candesartan and enalapril on brain ischemia through inhibition of oxidative stress. Neuropharmacology. 2006;51:822–8.PubMedCrossRef Hamai M, Iwai M, Ide A, Tomochika H, Tomono Y, Mogi M, et al. Comparison of inhibitory action of candesartan and enalapril on brain ischemia through inhibition of oxidative stress. Neuropharmacology. 2006;51:822–8.PubMedCrossRef
19.
Zurück zum Zitat El-Remessy AB, Al-Shabrawey M, Platt DH, Bartoli M, Behzadian MA, Ghaly N, et al. Peroxynitrite mediates VEGF’s angiogenic signal and function via a nitration-independent mechanism in endothelial cells. FASEB J. 2007;21:2528–39.PubMedCrossRef El-Remessy AB, Al-Shabrawey M, Platt DH, Bartoli M, Behzadian MA, Ghaly N, et al. Peroxynitrite mediates VEGF’s angiogenic signal and function via a nitration-independent mechanism in endothelial cells. FASEB J. 2007;21:2528–39.PubMedCrossRef
20.
Zurück zum Zitat Reeves MJ, Arora S, Broderick JP, Frankel M, Heinrich JP, Hickenbottom S, et al. Acute stroke care in the US: results from 4 pilot prototypes of the Paul Coverdell National Acute Stroke Registry. Stroke. 2005;36:1232–40.PubMedCrossRef Reeves MJ, Arora S, Broderick JP, Frankel M, Heinrich JP, Hickenbottom S, et al. Acute stroke care in the US: results from 4 pilot prototypes of the Paul Coverdell National Acute Stroke Registry. Stroke. 2005;36:1232–40.PubMedCrossRef
21.
Zurück zum Zitat Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, et al. The ACCESS study: evaluation of acute candesartan cilexitil therapy in stroke survivors. Stroke. 2003;34:1699–703.PubMedCrossRef Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, et al. The ACCESS study: evaluation of acute candesartan cilexitil therapy in stroke survivors. Stroke. 2003;34:1699–703.PubMedCrossRef
Metadaten
Titel
Acute Treatment with Candesartan Reduces Early Injury After Permanent Middle Cerebral Artery Occlusion
verfasst von
Weihua Guan
Anna Kozak
Azza B. El-Remessy
Maribeth H. Johnson
Bindu A. Pillai
Susan C. Fagan
Publikationsdatum
01.06.2011
Verlag
Springer-Verlag
Erschienen in
Translational Stroke Research / Ausgabe 2/2011
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-010-0061-1

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