Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia

• Verfasst von: Pham, Mirko [VerfasserIn]
• Verfasst von: Helluy, Xavier [VerfasserIn]
• Verfasst von: Kleinschnitz, Christoph [VerfasserIn]
• Verfasst von: Kraft, Peter [VerfasserIn]
• Verfasst von: Bartsch, Andreas J. [VerfasserIn]
• Verfasst von: Jakob, Peter [VerfasserIn]
• Verfasst von: Nieswandt, Bernhard [VerfasserIn]
• Verfasst von: Bendszus, Martin [VerfasserIn]
• Verfasst von: Stoll, Guido [VerfasserIn]
• Titel: Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia
• Titelzusatz: an MRI study at 17.6 Tesla
• Verf.angabe: Mirko Pham, Xavier Helluy, Christoph Kleinschnitz, Peter Kraft, Andreas J. Bartsch, Peter Jakob, Bernhard Nieswandt, Martin Bendszus, Guido Stoll
• E-Jahr: 2011
• Jahr: April 1, 2011
• Umfang: 8 S.
• Fussnoten: Gesehen am 13.12.2022
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2011
• Band/Heft Quelle: 6(2011), 4, Artikel-ID e18386, Seite 1-8
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0018386
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Animals
• Sach-SW: Anti-Inflammatory Agents
• Sach-SW: Cerebral Cortex
• Sach-SW: Cerebrovascular Circulation
• Sach-SW: Disease Progression
• Sach-SW: Immunoglobulin Fab Fragments
• Sach-SW: Infarction, Middle Cerebral Artery
• Sach-SW: Magnetic Resonance Imaging
• Sach-SW: Male
• Sach-SW: Mice
• Sach-SW: Platelet Glycoprotein GPIb-IX Complex
• Sach-SW: Time Factors
• K10plus-PPN: 1826858229

Abstract

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.