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Front. Neurosci. | doi: 10.3389/fnins.2019.00737

Insights from Dynamic Neuro-Immune Imaging on Murine Immune Responses to CNS Damage

  • 1Department of Medicine, Vanderbilt University Medical Center, United States
  • 2Department of Pathology, School of Medicine, Case Western Reserve University, United States
  • 3Department of Pediatrics, School of Medicine, Case Western Reserve University, United States
  • 4Pediatric, Pathology, Biomedical Engineering and General Medical Sciences, School of Medicine, Case Western Reserve University, United States

Technological advances in 2-Photon Laser Scanning Microscopy (2P-LSM) have allowed novel insights into in vivo immune response in a variety of tissue microenvironments. While imaging of peripheral tissues has provided an abundance of data with regards to immune cell dynamics, central nervous system (CNS) imaging is comparatively inhibited by tissue accessibility and manipulation. Despite these limitations, the results of dynamic intravital neuro-immune imaging thus far have provided foundational insights into basic CNS biology. Utilizing a combination of intravital and ex vivo 2P-LSM we have observed novel pathways allowing immune cells, stromal cells, cancer cells and proteins to communicate between the CNS parenchyma and peripheral vasculature. Similar to what has been reported in the intestinal tract, we have visualized myeloid cells extend dendritic processes across the blood brain barrier (BBB) into pial blood vessels. Furthermore, transient vessel leaks seen during systemic inflammation provide opportunities for cellular protein to be exchanged between the periphery and CNS. These insights provide new, visual information regarding immune surveillance and antigen presentation within the CNS. Furthermore, when combining intravital 2P-LSM and microfluidic devices complexed with mathematical modeling, we are gaining new insights into the intravascular behavior of circulating immune cells. This new knowledge into the basic mechanisms by which cells migrate to and interact with the CNS provide important considerations for the design of neuroelectric devices that have the potential to connect the peripheral-neural microenvironments in a unique, artificial interface.

Keywords: two-photon microscopy, Microglia, CNS, immune response, innate & adaptive immune response, Tissue microenvironment, Blood-Brain Barrier, vascular crawling, neural electrical recordings

Received: 15 Feb 2019; Accepted: 02 Jul 2019.

Edited by:

Ulrich G. Hofmann, Freiburg University Medical Center, Germany

Reviewed by:

Renaud B. Jolivet, Université de Genève, Switzerland
Naoto Kawakami, Ludwig Maximilian University of Munich, Germany  

Copyright: © 2019 Dorand, Dixon, Petrosiute and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Alex Y. Huang, School of Medicine, Case Western Reserve University, Pediatric, Pathology, Biomedical Engineering and General Medical Sciences, Cleveland, 44106-7288, Ohio, United States, Alex.Y.Huang@case.edu