Non-invasive near-infrared fluorescence imaging of the neutrophil response in a mouse model of transient cerebral ischaemia.

Vaas, Markus; Enzmann, Gaby; Périnat, Therese; Siler, Ulrich; Reichenbach, Janine; Licha, Kai; Kipar, Anja; Rudin, Markus; Engelhardt, Britta; Klohs, Jan (2017). Non-invasive near-infrared fluorescence imaging of the neutrophil response in a mouse model of transient cerebral ischaemia. Journal of cerebral blood flow and metabolism, 37(8), pp. 2833-2847. Nature Publishing Group 10.1177/0271678X16676825

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Near-infrared fluorescence (NIRF) imaging enables non-invasive monitoring of molecular and cellular processes in live animals. Here we demonstrate the suitability of NIRF imaging to investigate the neutrophil response in the brain after transient middle cerebral artery occlusion (tMCAO). We established procedures for ex vivo fluorescent labelling of neutrophils without affecting their activation status. Adoptive transfer of labelled neutrophils in C57BL/6 mice before surgery resulted in higher fluorescence intensities over the ischaemic hemisphere in tMCAO mice with NIRF imaging when compared with controls, corroborated by ex vivo detection of labelled neutrophils using fluorescence microscopy. NIRF imaging showed that neutrophils started to accumulate immediately after tMCAO, peaking at 18 h, and were still visible until 48 h after reperfusion. Our data revealed accumulation of neutrophils also in extracranial tissue, indicating damage in the external carotid artery territory in the tMCAO model. Antibody-mediated inhibition of α4-integrins did reduce fluorescence signals at 18 and 24, but not at 48 h after reperfusion, compared with control treatment animals. Antibody treatment reduced cerebral lesion volumes by 19%. In conclusion, the non-invasive nature of NIRF imaging allows studying the dynamics of neutrophil recruitment and its modulation by targeted interventions in the mouse brain after transient experimental cerebral ischaemia.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine

UniBE Contributor:

Enzmann, Gaby; Périnat, Therese and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0271-678X

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 May 2017 11:14

Last Modified:

30 Jul 2017 01:30

Publisher DOI:

10.1177/0271678X16676825

PubMed ID:

27789786

Uncontrolled Keywords:

Cerebral ischaemia; external carotid artery; middle cerebral artery occlusion; mouse; near-infrared fluorescence imaging; neutrophils

BORIS DOI:

10.7892/boris.95347

URI:

https://boris.unibe.ch/id/eprint/95347

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