| Title |
The neurovascular unit as a selective barrier to polymorphonuclear granulocyte (PMN) infiltration into the brain after ischemic injury
|
|---|---|
| Published in |
Acta Neuropathologica, December 2012
|
| DOI | 10.1007/s00401-012-1076-3 |
| Pubmed ID | |
| Authors |
Gaby Enzmann, Caroline Mysiorek, Roser Gorina, Yu-Jung Cheng, Sharang Ghavampour, Melanie-Jane Hannocks, Vincent Prinz, Ulrich Dirnagl, Matthias Endres, Marco Prinz, Rudi Beschorner, Patrick N. Harter, Michel Mittelbronn, Britta Engelhardt, Lydia Sorokin |
| Abstract |
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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Italy | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 209 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | <1% |
| Portugal | 1 | <1% |
| Brazil | 1 | <1% |
| Korea, Republic of | 1 | <1% |
| Belgium | 1 | <1% |
| Czechia | 1 | <1% |
| Unknown | 202 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 41 | 20% |
| Researcher | 28 | 13% |
| Student > Master | 22 | 11% |
| Student > Doctoral Student | 17 | 8% |
| Student > Postgraduate | 16 | 8% |
| Other | 45 | 22% |
| Unknown | 40 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 49 | 23% |
| Medicine and Dentistry | 41 | 20% |
| Agricultural and Biological Sciences | 31 | 15% |
| Immunology and Microbiology | 14 | 7% |
| Biochemistry, Genetics and Molecular Biology | 10 | 5% |
| Other | 17 | 8% |
| Unknown | 47 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 March 2014.
All research outputs
#2,792,620
of 22,747,498 outputs
Outputs from Acta Neuropathologica
#705
of 2,363 outputs
Outputs of similar age
#29,603
of 280,646 outputs
Outputs of similar age from Acta Neuropathologica
#3
of 15 outputs
Altmetric has tracked 22,747,498 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,363 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.4. This one has gotten more attention than average, scoring higher than 70% of its peers.
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We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.