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Perspective ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00582

Endothelial targeted strategies to combat oxidative stress: improving outcomes in traumatic brain injury

 Evan M. Lutton1, S K. Farney2, Allison M. Andrews1, Vladimir V. Shuvaev3, Gwo-Yu Chuang2, Vladimir R. Muzykantov3 and  Servio H. Ramirez1, 4, 5*
  • 1Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, United States
  • 2Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), United States
  • 3Department of Systems Pharmacology and Translational Therapeutics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, United States
  • 4Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, United States
  • 5Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, United States

The endothelium is a thin monolayer of specialized cells that lines the luminal wall of blood vessels and constitutes the critical innermost portion of the physical barrier between the blood and the brain termed the blood-brain barrier (BBB). Aberrant changes in the endothelium occur in many neuropathological states, including those with high morbidity and mortality that lack targeted therapeutic interventions, such as traumatic brain injury (TBI). Utilizing ligands of surface determinants expressed on brain endothelium to target and combat injury mechanisms at damaged endothelium offers a new approach to the study of TBI and new avenues for clinical advancement. Many factors influence the targets that are expressed on endothelium. Therefore, the optimization of binding sites and ideal design features of nanocarriers are controllable factors that permit the engineering of nanotherapeutic agents with applicability that is specific to a known disease state. Following TBI, damaged endothelial cells upregulate cell adhesion molecules, including ICAM-1, and are key sites of reactive oxygen species (ROS) generation, including hydrogen peroxide. Reactive oxygen species along with pro-inflammatory mediators are known to contribute to endothelial damage and loss of BBB integrity. The use of targeted endothelial nanomedicine, with conjugates of the antioxidant enzyme catalase linked to anti-ICAM-1 antibodies, has recently been demonstrated to minimize oxidative stress at the BBB and reduce neuropathological outcomes following TBI. Here, we discuss targeted endothelial nanomedicine and its potential to provide benefits in TBI outcomes and future directions of this approach.

Keywords: Nanomedicine, Endothelial immunotargeting, Neuroinflammation, Blood-brain barrer, Traumatic Brain Injury, Oxidative Stress

Received: 11 Jan 2019; Accepted: 17 May 2019.

Edited by:

András Büki, University of Pécs, Hungary

Reviewed by:

Maria A. Deli, Biological Research Centre (MTA), Hungarian Academy of Sciences, Hungary
Peter Toth, University of Pécs, Hungary  

Copyright: © 2019 Lutton, Farney, Andrews, Shuvaev, Chuang, Muzykantov and Ramirez. 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. Servio H. Ramirez, Lewis Katz School of Medicine, Temple University, Department of Pathology and Laboratory Medicine, Philadelphia, 19140, Pennsylvania, United States, servio@temple.edu