Monocyte chemoattractant protein-1-deficiency results in altered blood-brain barrier breakdown after experimental stroke.

Abstract

Stroke-induced blood-brain barrier (BBB)-disruption can contribute to further progression of cerebral damage. There is rising evidence for a strong involvement of chemokines in postischemic BBB-breakdown. In a previous study, we showed that monocyte chemoattractant protein-1 (MCP-1)-deficiency results in a markedly reduced inflammatory reaction with decreased levels of interleukin-6, interleukin-1β, and granulocyte colony-stimulating factor after experimental stroke. With MCP-1 as one of the key players in stroke-induced inflammation, in this study, we investigated the influence of MCP-1 on poststroke BBB-disruption as well as transcription/translation of BBB-related genes/proteins after cerebral ischemia. Sixteen wild-type and 16 MCP-1(-/-) mice were subjected to 30 minutes of middle cerebral artery occlusion. By injecting high molecular-tracer, we compared the degree of BBB-disruption after middle cerebral artery occlusion. Real-time polymerase chain reactions and Western blot technique were used to compare tight-junction gene expression, protein secretion, and BBB-leakage. Here, we report that MCP-1-deficiency results in a reduced BBB-leakage and a diminished expression of BBB-related genes occludin, zonula occludens-1, and zonula occludens-2. Real-time polymerase chain reactions and Western blot analysis revealed elevated claudin-5-levels in MCP-1(-/-) animals. MCP-1-deficiency resulted in reduced infarct sizes and an increased vascular accumulation of fluorescein-isothiocyanate-albumin. The results of the study provide further insights into the molecular mechanisms of BBB-opening and may help to better understand the mechanisms of infarct development after cerebral ischemia.