In vivo temporal and spatial profile of leukocyte adhesion and migration after experimental traumatic brain injury in mice

Journal of Neuroinflammation

Nikolaus Plesnila⁴  Seong-Woong Kim¹  Raimund Trabold²  Niamh B McGarry¹  Ricarda Zimmermann²  Susanne M Schwarzmaier³ 

[1] Department of Neurodegeneration, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephen’s Green, Dublin 2, Ireland;Institute for Surgical Research in the Walter-Brendel-Centre of Experimental Medicine, University of Munich Medical Center, Marchioninistr. 15, 81377 Munich, Germany;Current address: Department of Anesthesiology, University of Munich Medical Center, Marchioninistr. 15, 81377 Munich, Germany;Institute for Stroke and Dementia Research (ISD), University of Munich Medical Center, Max-Lebsche Platz 30, Munich, 81377, Germany

关键词: Mice;    In vivo;    Intravital microscopy;    2-photon microscopy;    Leukocyte-platelet aggregates;    Leukocyte adhesion;    Secondary brain damage;    Brain trauma;    Inflammation;    Leukocytes;   

Others  :  1160017
DOI  :  10.1186/1742-2094-10-32

 received in 2012-08-01, accepted in 2013-02-05,  发布年份 2013

【 摘 要 】

Background

Leukocytes are believed to be involved in delayed cell death following traumatic brain injury (TBI). However, data demonstrating that blood-borne inflammatory cells are present in the injured brain prior to the onset of secondary brain damage have been inconclusive. We therefore investigated both the interaction between leukocytes and the cerebrovascular endothelium using in vivo imaging and the accumulation of leukocytes in the penumbra following experimentally induced TBI.

Methods

Experimental TBI was induced in C57/Bl6 mice (n = 42) using the controlled cortical impact (CCI) injury model, and leukocyte-endothelium interactions (LEI) were quantified using both intravital fluorescence microscopy (IVM) of superficial vessels and 2-photon microscopy of cortical vessels for up to 14 h post-CCI. In a separate experimental group, leukocyte accumulation and secondary lesion expansion were analyzed in mice that were sacrificed 15 min, 2, 6, 12, 24, or 48 h after CCI (n = 48). Finally, leukocyte adhesion was blocked with anti-CD18 antibodies, and the effects on LEI and secondary lesion expansion were determined 16 (n = 12) and 24 h (n = 21), respectively, following TBI.

Results

One hour after TBI leukocytes and leukocyte-platelet aggregates started to roll on the endothelium of pial venules, whereas no significant LEI were observed in pial arterioles or in sham-operated mice. With a delay of >4 h, leukocytes and aggregates did also firmly adhere to the venular endothelium. In deep cortical vessels (250 μm) LEIs were much less pronounced. Transmigration of leukocytes into the brain parenchyma only became significant after the tissue became necrotic. Treatment with anti-CD18 antibodies reduced adhesion by 65%; however, this treatment had no effect on secondary lesion expansion.

Conclusions

LEI occurred primarily in pial venules, whereas little or no LEI occurred in arterioles or deep cortical vessels. Inhibiting LEI did not affect secondary lesion expansion. Importantly, the majority of migrating leukocytes entered the injured brain parenchyma only after the tissue became necrotic. Our results therefore suggest that neither intravascular leukocyte adhesion nor the migration of leukocytes into cerebral tissue play a significant role in the development of secondary lesion expansion following TBI.

【 授权许可】

   
2013 Schwarzmaier et al.; licensee BioMed Central Ltd.

【 图 表 】

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