Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury
Abstract Traumatic brain injury (TBI) contributes to one third of injury related deaths in the US. Treatment strategies for TBI are supportive, and the pathophysiology is not fully understood. Secondary mechanisms of injury in TBI, such as oxidative stress and inflammation, are points at which inter...
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doaj-8c574c0d411e41d5b652a7758170ba4f2020-12-08T01:34:23ZengNature Publishing GroupScientific Reports2045-23222017-06-017111510.1038/s41598-017-03309-4Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injuryEvan M. Lutton0Roshanak Razmpour1Allison M. Andrews2Lee Anne Cannella3Young-Jin Son4Vladimir V. Shuvaev5Vladimir R. Muzykantov6Servio H. Ramirez7Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple UniversityDepartment of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple UniversityDepartment of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple UniversityDepartment of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple UniversityShriners Hospitals Pediatric Research Center, The Lewis Katz School of Medicine at Temple UniversityDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of PennsylvaniaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of PennsylvaniaDepartment of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple UniversityAbstract Traumatic brain injury (TBI) contributes to one third of injury related deaths in the US. Treatment strategies for TBI are supportive, and the pathophysiology is not fully understood. Secondary mechanisms of injury in TBI, such as oxidative stress and inflammation, are points at which intervention may reduce neuropathology. Evidence suggests that reactive oxygen species (ROS) propagate blood-brain barrier (BBB) hyperpermeability and inflammation following TBI. We hypothesized that targeted detoxification of ROS may improve the pathological outcomes of TBI. Following TBI, endothelial activation results in a time dependent increase in vascular expression of ICAM-1. We conjugated catalase to anti-ICAM-1 antibodies and administered the conjugate to 8 wk old C57BL/6J mice 30 min after moderate controlled cortical impact injury. Results indicate that catalase targeted to ICAM-1 reduces markers of oxidative stress, preserves BBB permeability, and attenuates neuropathological indices more effectively than non-targeted catalase and anti-ICAM-1 antibody alone. Furthermore, the study of microglia by two-photon microscopy revealed that anti-ICAM-1/catalase prevents the transition of microglia to an activated phenotype. These findings demonstrate the use of a targeted antioxidant enzyme to interfere with oxidative stress mechanisms in TBI and provide a proof-of-concept approach to improve acute TBI management that may also be applicable to other neuroinflammatory conditions.https://doi.org/10.1038/s41598-017-03309-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Evan M. Lutton Roshanak Razmpour Allison M. Andrews Lee Anne Cannella Young-Jin Son Vladimir V. Shuvaev Vladimir R. Muzykantov Servio H. Ramirez |
spellingShingle |
Evan M. Lutton Roshanak Razmpour Allison M. Andrews Lee Anne Cannella Young-Jin Son Vladimir V. Shuvaev Vladimir R. Muzykantov Servio H. Ramirez Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury Scientific Reports |
author_facet |
Evan M. Lutton Roshanak Razmpour Allison M. Andrews Lee Anne Cannella Young-Jin Son Vladimir V. Shuvaev Vladimir R. Muzykantov Servio H. Ramirez |
author_sort |
Evan M. Lutton |
title |
Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury |
title_short |
Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury |
title_full |
Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury |
title_fullStr |
Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury |
title_full_unstemmed |
Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury |
title_sort |
acute administration of catalase targeted to icam-1 attenuates neuropathology in experimental traumatic brain injury |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-06-01 |
description |
Abstract Traumatic brain injury (TBI) contributes to one third of injury related deaths in the US. Treatment strategies for TBI are supportive, and the pathophysiology is not fully understood. Secondary mechanisms of injury in TBI, such as oxidative stress and inflammation, are points at which intervention may reduce neuropathology. Evidence suggests that reactive oxygen species (ROS) propagate blood-brain barrier (BBB) hyperpermeability and inflammation following TBI. We hypothesized that targeted detoxification of ROS may improve the pathological outcomes of TBI. Following TBI, endothelial activation results in a time dependent increase in vascular expression of ICAM-1. We conjugated catalase to anti-ICAM-1 antibodies and administered the conjugate to 8 wk old C57BL/6J mice 30 min after moderate controlled cortical impact injury. Results indicate that catalase targeted to ICAM-1 reduces markers of oxidative stress, preserves BBB permeability, and attenuates neuropathological indices more effectively than non-targeted catalase and anti-ICAM-1 antibody alone. Furthermore, the study of microglia by two-photon microscopy revealed that anti-ICAM-1/catalase prevents the transition of microglia to an activated phenotype. These findings demonstrate the use of a targeted antioxidant enzyme to interfere with oxidative stress mechanisms in TBI and provide a proof-of-concept approach to improve acute TBI management that may also be applicable to other neuroinflammatory conditions. |
url |
https://doi.org/10.1038/s41598-017-03309-4 |
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