Advances in imaging of new targets for pharmacological intervention in stroke: real-time tracking of T-cells in the ischaemic brain

Br J Pharmacol. 2010 Feb;159(4):808-11. doi: 10.1111/j.1476-5381.2009.00527.x. Epub 2009 Dec 10.

Abstract

Background and purpose: T-cells may play a role in the evolution of ischaemic damage and repair, but the ability to image these cells in the living brain after a stroke has been limited. We aim to extend the technique of real-time in situ brain imaging of T-cells, previously shown in models of immunological diseases, to models of experimental stroke.

Experimental approach: Male C57BL6 mice (6-8 weeks) (n= 3) received a total of 2-5 x 10(6) carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled lymphocytes from donor C57BL6 mice via i.v. injection by adoptive transfer. Twenty-four hours later, recipient mice underwent permanent left distal middle cerebral artery occlusion (MCAO) by electrocoagulation or by sham surgery under isoflurane anaesthesia. Female hCD2-green fluorescent protein (GFP) transgenic mice that exhibit GFP-labelled T-cells underwent MCAO. At 24 or 48 h post-MCAO, a sagittal brain slice (1500 microm thick) containing cortical branches of the occluded middle cerebral artery (MCA) was dissected and used for multiphoton laser scanning microscopy (MPLSM).

Key results: Our results provide direct observations for the first time of dynamic T-cell behaviour in living brain tissue in real time and herein proved the feasibility of MPLSM for ex vivo live imaging of immune response after experimental stroke.

Conclusions and implications: It is hoped that these advances in the imaging of immune cells will provide information that can be harnessed to a therapeutic advantage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Brain / immunology
  • Brain / metabolism*
  • Disease Models, Animal
  • Feasibility Studies
  • Female
  • Fluoresceins / metabolism
  • Fluorescent Dyes / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Infarction, Middle Cerebral Artery / immunology
  • Infarction, Middle Cerebral Artery / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton*
  • Molecular Imaging*
  • Molecular Probe Techniques*
  • Succinimides / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / transplantation
  • Time Factors

Substances

  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Fluoresceins
  • Fluorescent Dyes
  • Succinimides
  • Green Fluorescent Proteins