Article
Ultraearly reperfusion induces blood brain barrier disruption during focal ischemia in rats
Kurzzeitige Reperfusion verstärkt die Störung der Blut-Hirn-Schranke bei permanenter fokaler Ischämie
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Published: | May 4, 2005 |
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Outline
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Objective
Unintentional reperfusion is considered a complication in a number of ischemia models. In the following study we evaluated whether a short-term reperfusion affects ischemic volume and blood brain barrier (BBB) after permanent focal ischemia in rats.
Methods
Focal brain ischemia was induced in male SD rats using the intraluminal filament method. In groups 1, 2, and 3 a 20 second reperfusion period was allowed 0.5, 2 and 10 minutes after thread occlusion. In control animals reperfusion was omitted. Twenty-four hours after permanent middle cerebral artery occlusion animals were killed and the infarct volume and swelling examined on serial coronar silver nitrate stained sections. Expression of vascular endothelial growth factor (VEGF) and matrix-metalloproteinases (MMP) 2 and 9 was investigated using RT-PCR and zymography.
Results
Short reperfusion already two minutes after thread occlusion lead to a significant increase of the ischemic volume (control animals: 423±32 mm3, group 1: 428±62 mm3, group 2: 547±48 mm3*, group 3: 592±74 mm3*, * p<0,05 vs. control animals) and swelling (control animals: 15,5±10,8%, group 1: 24,7±7,0%, group 2: 36,7±4,8%*, group 3: 33,8±4,9%*, *p<0,05 vs. control animals) after 24 hours permanent ischemia. Swelling contributed significantly to the increased ischemic volume after reperfusion. The ratio of ipsilateral/contralateral VEGF and MMP 9 content tends to result in increased activities (VEGF: group 4: 1.67±0.44 vs control: 1.06±0.10, p<0.1; MMP 9: group4: 4.40±1.54 vs control: 2.42±0.87, p<0.1).
Conclusions
Early transient reperfusion may be causal for increased disruption of the BBB in stroke patients. Thus screening for mechanisms of reperfusion injury may be worthwhile to detect patients at risk for BBB damage before initiating reperfusion therapy, which is associated with a further disruption of the BBB and subsequent intracerebral bleeding.