PMID- 23269317
OWN - NLM
STAT- MEDLINE
DCOM- 20130904
LR  - 20240330
IS  - 1432-0533 (Electronic)
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 125
IP  - 3
DP  - 2013 Mar
TI  - The neurovascular unit as a selective barrier to polymorphonuclear granulocyte 
      (PMN) infiltration into the brain after ischemic injury.
PG  - 395-412
LID - 10.1007/s00401-012-1076-3 [doi]
AB  - The migration of polymorphonuclear granulocytes (PMN) into the brain parenchyma 
      and release of their abundant proteases are considered the main causes of 
      neuronal cell death and reperfusion injury following ischemia. Yet, therapies 
      targeting PMN egress have been largely ineffective. To address this discrepancy 
      we investigated the temporo-spatial localization of PMNs early after transient 
      ischemia in a murine transient middle cerebral artery occlusion (tMCAO) model and 
      human stroke specimens. Using specific markers that distinguish PMN (Ly6G) from 
      monocytes/macrophages (Ly6C) and that define the cellular and basement membrane 
      boundaries of the neurovascular unit (NVU), histology and confocal microscopy 
      revealed that virtually no PMNs entered the infarcted CNS parenchyma. Regardless 
      of tMCAO duration, PMNs were mainly restricted to luminal surfaces or 
      perivascular spaces of cerebral vessels. Vascular PMN accumulation showed no 
      spatial correlation with increased vessel permeability, enhanced expression of 
      endothelial cell adhesion molecules, platelet aggregation or release of 
      neutrophil extracellular traps. Live cell imaging studies confirmed that oxygen 
      and glucose deprivation followed by reoxygenation fail to induce PMN migration 
      across a brain endothelial monolayer under flow conditions in vitro. The absence 
      of PMN infiltration in infarcted brain tissues was corroborated in 25 human 
      stroke specimens collected at early time points after infarction. Our 
      observations identify the NVU rather than the brain parenchyma as the site of PMN 
      action after CNS ischemia and suggest reappraisal of targets for therapies to 
      reduce reperfusion injury after stroke.
FAU - Enzmann, Gaby
AU  - Enzmann G
AD  - Theodor Kocher Institute, University of Bern, Freiestrasse 1, 3012, Bern, 
      Switzerland.
FAU - Mysiorek, Caroline
AU  - Mysiorek C
FAU - Gorina, Roser
AU  - Gorina R
FAU - Cheng, Yu-Jung
AU  - Cheng YJ
FAU - Ghavampour, Sharang
AU  - Ghavampour S
FAU - Hannocks, Melanie-Jane
AU  - Hannocks MJ
FAU - Prinz, Vincent
AU  - Prinz V
FAU - Dirnagl, Ulrich
AU  - Dirnagl U
FAU - Endres, Matthias
AU  - Endres M
FAU - Prinz, Marco
AU  - Prinz M
FAU - Beschorner, Rudi
AU  - Beschorner R
FAU - Harter, Patrick N
AU  - Harter PN
FAU - Mittelbronn, Michel
AU  - Mittelbronn M
FAU - Engelhardt, Britta
AU  - Engelhardt B
FAU - Sorokin, Lydia
AU  - Sorokin L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121227
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Ly)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Ly-6C antigen, mouse)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Antigens, Ly/metabolism
MH  - Blood Vessels/pathology/physiopathology
MH  - Blood-Brain Barrier/pathology/*physiopathology
MH  - Brain/*pathology
MH  - Cell Adhesion Molecules/metabolism
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Endothelium/pathology
MH  - Functional Laterality
MH  - Gene Expression Regulation/physiology
MH  - Glucose/deficiency
MH  - Granulocytes/*pathology
MH  - Humans
MH  - Hypoxia
MH  - Infarction, Middle Cerebral Artery/*immunology/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Oxygen/administration & dosage
PMC - PMC3578720
EDAT- 2012/12/28 06:00
MHDA- 2013/09/05 06:00
PMCR- 2012/12/27
CRDT- 2012/12/28 06:00
PHST- 2012/08/23 00:00 [received]
PHST- 2012/12/14 00:00 [accepted]
PHST- 2012/12/14 00:00 [revised]
PHST- 2012/12/28 06:00 [entrez]
PHST- 2012/12/28 06:00 [pubmed]
PHST- 2013/09/05 06:00 [medline]
PHST- 2012/12/27 00:00 [pmc-release]
AID - 1076 [pii]
AID - 10.1007/s00401-012-1076-3 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2013 Mar;125(3):395-412. doi: 10.1007/s00401-012-1076-3. Epub 
      2012 Dec 27.