Monocyte Chemoattractant Protein-1―Deficiency Results in Altered Blood―Brain Barrier Breakdown After Experimental Stroke

• Published in: Stroke (1970) 2013-09, Vol.44 (9), p.2536-2544
• Main Authors: STRECKER, Jan-Kolja, MINNERUP, Jens, SCHÜTTE-NÜTGEN, Katharina, GESS, Burkhard, SCHÄBITZ, Wolf-Rüdiger, SCHILLING, Matthias
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; Blood-Brain Barrier - physiopathology; Chemokine CCL2 - deficiency; Chemokine CCL2 - genetics; Disease Models, Animal; Gene Expression Regulation - genetics; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Infarction, Middle Cerebral Artery - etiology; Infarction, Middle Cerebral Artery - genetics; Infarction, Middle Cerebral Artery - pathology; Inflammation - genetics; Inflammation - immunology; Inflammation - physiopathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Nervous system (semeiology, syndromes); Neurology; Protein Biosynthesis - genetics; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/strokeaha.111.000528

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.