Back to Search
Start Over
Neutrophil recruitment to the brain in mouse and human ischemic stroke
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Acta Neuropathol. 129(2) 239-57 (2014), ZENODO, Digital.CSIC
- Publication Year :
- 2014
- Publisher :
- Springer, 2014.
-
Abstract
- Neutrophils are rapidly recruited in response to local tissue infection or inflammation. Stroke triggers a strong inflammatory reaction but the relevance of neutrophils in the ischemic brain is not fully understood, particularly in the absence of reperfusion. We investigated brain neutrophil recruitment in two murine models of permanent ischemia induced by either cauterization of the distal portion of the middle cerebral artery (c-MCAo) or intraluminal MCA occlusion (il-MCAo), and three fatal cases of human ischemic stroke. Flow cytometry analyses revealed progressive neutrophil recruitment after c-MCAo, lesser neutrophil recruitment following il-MCAo, and absence of neutrophils after sham operation. Confocal microscopy identified neutrophils in the leptomeninges from 6 h after the occlusion, in the cortical basal lamina and cortical Virchow–Robin spaces from 15 h, and also in the cortical brain parenchyma at 24 h. Neutrophils showed signs of activation including histone-3 citrullination, chromatin decondensation, and extracellular projection of DNA and histones suggestive of extracellular trap formation. Perivascular neutrophils were identified within the entire cortical infarction following c-MCAo. After il-MCAo, neutrophils prevailed in the margins but not the center of the cortical infarct, and were intraluminal and less abundant in the striatum. The lack of collaterals to the striatum and a collapsed pial anastomotic network due to brain edema in large hemispheric infarctions could impair neutrophil trafficking in this model. Neutrophil extravasation at the leptomeninges was also detected in the human tissue. We concluded that neutrophils extravasate from the leptomeningeal vessels and can eventually reach the brain in experimental animal models and humans with prolonged arterial occlusion. © 2014, Springer-Verlag Berlin Heidelberg<br />Supported by the Spanish Ministries of Economy (SAF2011-30492) and Health (FIS PI12/01437), and FP7 EU projects ERANET-NEURON (PRI-PIMNEU-2011-1342) and InMIND (grant agreement no 278,850)
- Subjects :
- Male
Pathology
medicine.medical_specialty
Neutrophils
Ischemia
Fluorescent Antibody Technique
Inflammation
Pathology and Forensic Medicine
Brain Ischemia
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
medicine.artery
Parenchyma
medicine
Animals
Humans
cardiovascular diseases
Perivascular
Stroke
030304 developmental biology
Aged
Aged, 80 and over
0303 health sciences
Neutrophil extravasation
Mice, Inbred BALB C
Leptomeninges
Microscopy, Confocal
Rodent
business.industry
Brain
medicine.disease
Flow Cytometry
Disease Models, Animal
medicine.anatomical_structure
Neutrophil Infiltration
Middle cerebral artery
cardiovascular system
Basal lamina
Female
Neurology (clinical)
medicine.symptom
business
030217 neurology & neurosurgery
Human
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Acta Neuropathol. 129(2) 239-57 (2014), ZENODO, Digital.CSIC
- Accession number :
- edsair.doi.dedup.....7b9bbaaed51bddb639aece961e4a0cfc