Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia : an MRI study at 17.6 Tesla / Mirko Pham, Xavier Helluy, Christoph Kleinschnitz, Peter Kraft, Andreas J. Bartsch, Peter Jakob, Bernhard Nieswandt, Martin Bendszus, Guido Stoll
BACKGROUND: Inhibition of early platelet adhesion by blockade of glycoprotein-IB (GPIb) protects mice from ischemic stroke. To elucidate underlying mechanisms in-vivo, infarct development was followed by ultra-high field MRI at 17.6 Tesla. - METHODS: Cerebral infarction was induced by transient-middle-cerebral-artery-occlusion (tMCAO) for 1 hour in C57/BL6 control mice (N=10) and mice treated with 100 µg Fab-fragments of the GPIb blocking antibody p0p/B 1 h after tMCAO (N=10). To control for the effect of reperfusion, additional mice underwent permanent occlusion and received anti-GPIb treatment (N=6; pMCAO) or remained without treatment (N=3; pMCAO). MRI 2 h and 24 h after MCAO measured cerebral-blood-flow (CBF) by continuous arterial-spin labelling, the apparent-diffusion-coefficient (ADC), quantitative-T2 and T2-weighted imaging. All images were registered to a standard mouse brain MRI atlas and statistically analysed voxel-wise, and by cortico-subcortical ROI analysis. - RESULTS: Anti-GPIb treatment led to a relative increase of postischemic CBF vs. controls in the cortical territory of the MCA (2 h: 44.2±6.9 ml/100 g/min versus 24 h: 60.5±8.4; p=0.0012, F((1,18))=14.63) after tMCAO. Subcortical CBF 2 h after tMCAO was higher in anti-GPIb treated animals (45.3±5.9 vs. controls: 33.6±4.3; p=0.04). In both regions, CBF findings were clearly related to a lower probability of infarction (Cortex/Subcortex of treated group: 35%/65% vs. controls: 95%/100%) and improved quantitative-T2 and ADC. After pMCAO, anti-GPIb treated mice developed similar infarcts preceded by severe irreversible hypoperfusion as controls after tMCAO indicating dependency of stroke protection on reperfusion. - CONCLUSION: Blockade of platelet adhesion by anti-GPIb-Fab-fragments results in substantially improved CBF early during reperfusion. This finding was in exact spatial correspondence with the prevention of cerebral infarction and indicates in-vivo an increased patency of the microcirculation. Thus, progression of infarction during early ischemia and reperfusion can be mitigated by anti-platelet treatment..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
April 1, 2011 2011 |
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| Erschienen: |
April 1, 2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
PLOS ONE - 6(2011), 4, Artikel-ID e18386, Seite 1-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pham, Mirko, 1978- [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Anmerkungen: |
Gesehen am 13.12.2022 |
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| Umfang: |
8 |
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| doi: |
10.1371/journal.pone.0018386 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
1826858229 |
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| 245 | 1 | 0 | |a Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia |b an MRI study at 17.6 Tesla |c Mirko Pham, Xavier Helluy, Christoph Kleinschnitz, Peter Kraft, Andreas J. Bartsch, Peter Jakob, Bernhard Nieswandt, Martin Bendszus, Guido Stoll |
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| 520 | |a BACKGROUND: Inhibition of early platelet adhesion by blockade of glycoprotein-IB (GPIb) protects mice from ischemic stroke. To elucidate underlying mechanisms in-vivo, infarct development was followed by ultra-high field MRI at 17.6 Tesla. - METHODS: Cerebral infarction was induced by transient-middle-cerebral-artery-occlusion (tMCAO) for 1 hour in C57/BL6 control mice (N=10) and mice treated with 100 µg Fab-fragments of the GPIb blocking antibody p0p/B 1 h after tMCAO (N=10). To control for the effect of reperfusion, additional mice underwent permanent occlusion and received anti-GPIb treatment (N=6; pMCAO) or remained without treatment (N=3; pMCAO). MRI 2 h and 24 h after MCAO measured cerebral-blood-flow (CBF) by continuous arterial-spin labelling, the apparent-diffusion-coefficient (ADC), quantitative-T2 and T2-weighted imaging. All images were registered to a standard mouse brain MRI atlas and statistically analysed voxel-wise, and by cortico-subcortical ROI analysis. - RESULTS: Anti-GPIb treatment led to a relative increase of postischemic CBF vs. controls in the cortical territory of the MCA (2 h: 44.2±6.9 ml/100 g/min versus 24 h: 60.5±8.4; p=0.0012, F((1,18))=14.63) after tMCAO. Subcortical CBF 2 h after tMCAO was higher in anti-GPIb treated animals (45.3±5.9 vs. controls: 33.6±4.3; p=0.04). In both regions, CBF findings were clearly related to a lower probability of infarction (Cortex/Subcortex of treated group: 35%/65% vs. controls: 95%/100%) and improved quantitative-T2 and ADC. After pMCAO, anti-GPIb treated mice developed similar infarcts preceded by severe irreversible hypoperfusion as controls after tMCAO indicating dependency of stroke protection on reperfusion. - CONCLUSION: Blockade of platelet adhesion by anti-GPIb-Fab-fragments results in substantially improved CBF early during reperfusion. This finding was in exact spatial correspondence with the prevention of cerebral infarction and indicates in-vivo an increased patency of the microcirculation. Thus, progression of infarction during early ischemia and reperfusion can be mitigated by anti-platelet treatment. | ||
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| 650 | 4 | |a Cerebral Cortex | |
| 650 | 4 | |a Cerebrovascular Circulation | |
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| 650 | 4 | |a Infarction, Middle Cerebral Artery | |
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