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

Episode von Medizin - Open Access LMU - Teil 21/22 von Ludwig-Maximilians-Universität München · 1. Januar 2013

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 mu m) 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.

Weitere Episoden von „Medizin - Open Access LMU - Teil 21/22“

• A genotype-specific, randomized controlled behavioral intervention to improve the neuroemotional outcome of cardiac surgery: study protocol for a randomized controlled trial 1. Januar 2013
• A new web-based method for automated analysis of muscle histology 1. Januar 2013
• Acceptance of routine or case-based inquiry for intimate partner violence: a mixed method study 1. Januar 2013
• Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial 1. Januar 2013
• Aequilibrium prudentis: on the necessity for ethics and policy studies in the scientific and technological education of medical professionals 1. Januar 2013
• An AUC-based permutation variable importance measure for random forests 1. Januar 2013
• Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum 1. Januar 2013
• `Burden to others' as a public concern in advanced cancer: a comparative survey in seven European countries 1. Januar 2013
• Characterization of in vivo chemoresistant human hepatocellular carcinoma cells with transendothelial differentiation capacities 1. Januar 2013
• Conscious Presence and Self Control as a measure of situational awareness in soldiers - A validation study 1. Januar 2013
• Contrast enhanced transesophageal echocardiography in patients with atrial fibrillation referred to electrical cardioversion improves atrial thrombus detection and may reduce associated thromboembolic events 1. Januar 2013
• Current experience with applying the GRADE approach to public health interventions: an empirical study 1. Januar 2013
• Current management of patients hospitalized with community-acquired pneumonia across Europe: outcomes from REACH 1. Januar 2013
• Diversity of the var gene family of Indonesian Plasmodium falciparum isolates 1. Januar 2013
• A comparative analysis of the properties of regulated promoter systems commonly used for recombinant gene expression in Escherichia coli 1. Januar 2013

Alle Episoden von Medizin - Open Access LMU - Teil 21/22 · Mehr Bildung-Podcasts