gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Study on the effect of early hypoxia on ischemic brain damage

Untersuchungen zur pathophysiologischen Bedeutung der frühen Hypoxie für den ischämischen Hirngewebeschaden

Meeting Abstract

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  • corresponding author C. Heiser - Neurochirurgische Klinik, Universitätsklinikum Mannheim
  • L. Schilling - Neurochirurgische Klinik, Universitätsklinikum Mannheim

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocFR.03.02

The electronic version of this article is the complete one and can be found online at:

Published: April 11, 2007

© 2007 Heiser et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: In the pathophysiological sequelae of cerebral ischemia, a number of reaction pathways are thought to be involved including excitotoxic, apoptotic and inflammatory mechanisms. However, the contribution of the individual pathways is still a matter of debate. In the present study, we sought to characterize the role of tissue hypoxia on structural brain damage in a model of focal brain ischemia.

Methods: Male Sprague-Dawley rats underwent a permanent occlusion of the right middle cerebral artery (MCA) using an intraluminal filament inserted into the carotid artery. One hour before MCA occlusion, the animals received a bolus injection of pimonidazole (60 mg/100 g body weight). Immediately after establishing MCA occlusion, an artificial O2 carrier (Oxycyte, a second generation perfluorocarbone solution, 1 ml/100 g body weight) was injected (control animals: injection of saline) followed by breathing O2 for a maximum of 8 h (control animals breathing air). The animals were killed 2, 4, 8 or 24 h after MCA occlusion, the brain was removed and serially cut in coronal slices for immunohistochemical detection of pimonidazole adducts indicative of cellular hypoxia or silver nitrate staining for outlining of structural brain damage, respectively. The sections were scanned for volumetric analysis with appropriate correction for brain swelling.

Results: In the control group the volumes of ischemic damage / tissue hypoxia are (mean+SD) 247±20 / 276±19 mm3 (2 h), 263±19 / 310±41 mm3 (4 h), 315±33 / 373±37 mm3 (8 h), and 446±46 / 509±64 mm3 (24 h). The corresponding values for the treatment group are 202±28 / 247±13 mm3 (2 h), 223±14 / 258±20 mm3 (4 h), 267±13 / 291±19 mm3 (8 h), and 335±51 / 366±37 mm3 (24 h). In the treated animals the volume of necrosis was significantly (p<0.05) smaller than in controls at all time points, the volume of hypoxia only at 8 and 24 h after MCA occlusion.

Conclusions: An improvement of the O2 transport capacity by an artificial O2 carrier early after onset of ischemia resulted in a significant decrease in tissue damage. This effect was sustained even after ceasing this therapy. These results suggest that an early tissue hypoxia plays a significant role in the development of post-ischemic brain damage.