gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

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Histological appearance of endothelial factor VIII correlates with the duration and severity of infarct after ischemic stroke in the rat

Endotheliale Verteilung von Faktor VIII als potentieller Indikator für Dauer und Schweregrad von Ischämien in einem Schlaganfallmodell in der Ratte

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  • corresponding author B. Schatlo - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA
  • M. Merrill - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA
  • E. H. Oldfield - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA
  • R. M. Pluta - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 115

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2008/08dgnc383.shtml

Published: May 30, 2008

© 2008 Schatlo et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Objective: Infarct volume is often regarded as a surrogate marker for treatment success in experimental animal models of stroke. This surrogate marker continues to be used despite our knowledge about the differences in collateral vascularization between rodents and humans and the failure of “neuroprotective” substances to yield clinical benefit. Since thrombolysis with recombinant tissue plasminogen activator (rtPA) after stroke increases the risk of hemorrhagic transformation, substances with additional protective effects on vasculature may provide a promising avenue to treatment success. We evaluated morphometric assessment of cerebral microvasculature after ischemic stroke as a potential marker for treatment effect in models of ischemic stroke.

Methods: The study involved n=26 Sprague Dawley rats with 6 hours and n=33 rats with 2 hours of ischemia induced by middle cerebral artery occlusion (MCAO) followed by reperfusion and thrombolysis with rtPA. At 48 hours, the animals were sacrificed and brains were shock-frozen at -80 deg C. To quantify the morphological appearance of microvessels, one 10μm frozen section was obtained from bregma +1mm and stained with factor VIII. A blinded investigator identified vessels under the microscope and scores were attributed according to each slide using a grading scale developed at our institution for this purpose.

Results: Infarct volumes were significantly higher in the 6-hour than in the 2-hour ischemia group (p=0.04). Accordingly, factor VIII vessel morphology scores were lower after 6 hours of ischemia than in the 2-hour group (p=0.001).

Conclusions: Histological evaluation of factor VIII staining reflected the degree and duration of ischemic insult. Vessel morphology scores were lower in 6-hour group compared to 2 hours of MCAO, suggesting progression of endothelial cell death beyond 2 hours of ischemia which has been doubted by previous investigators. Thus, even two hours into ischemia a part of the cerebral microvasculature appears to be salvageable.