PMID- 23821228
OWN - NLM
STAT- MEDLINE
DCOM- 20131118
LR  - 20220318
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 44
IP  - 9
DP  - 2013 Sep
TI  - Monocyte chemoattractant protein-1-deficiency results in altered blood-brain 
      barrier breakdown after experimental stroke.
PG  - 2536-44
LID - 10.1161/STROKEAHA.111.000528 [doi]
AB  - BACKGROUND AND PURPOSE: 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-1beta, 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. 
      METHODS: 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. RESULTS: 
      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. CONCLUSIONS: 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.
FAU - Strecker, Jan-Kolja
AU  - Strecker JK
AD  - Department of Neurology, University of Munster, Albert-Schweitzer Campus A1, 
      Munster, Germany. strecker.jan@gmx.de
FAU - Minnerup, Jens
AU  - Minnerup J
FAU - Schutte-Nutgen, Katharina
AU  - Schutte-Nutgen K
FAU - Gess, Burkhard
AU  - Gess B
FAU - Schabitz, Wolf-Rudiger
AU  - Schabitz WR
FAU - Schilling, Matthias
AU  - Schilling M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130702
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/*metabolism/pathology/physiopathology
MH  - Chemokine CCL2/*deficiency/*genetics
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/genetics
MH  - Infarction, Middle Cerebral Artery/etiology/*genetics/pathology
MH  - Inflammation/genetics/immunology/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Protein Biosynthesis/genetics
OTO - NOTNLM
OT  - CCL2, claudin-5
OT  - brain ischemia
OT  - brain-blood barrier
OT  - inflammation
OT  - occludin
EDAT- 2013/07/04 06:00
MHDA- 2013/11/19 06:00
CRDT- 2013/07/04 06:00
PHST- 2013/07/04 06:00 [entrez]
PHST- 2013/07/04 06:00 [pubmed]
PHST- 2013/11/19 06:00 [medline]
AID - STROKEAHA.111.000528 [pii]
AID - 10.1161/STROKEAHA.111.000528 [doi]
PST - ppublish
SO  - Stroke. 2013 Sep;44(9):2536-44. doi: 10.1161/STROKEAHA.111.000528. Epub 2013 Jul 
      2.