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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Evan M. Lutton, Roshanak Razmpour, Allison M. Andrews, Lee Anne Cannella, Young-Jin Son, Vladimir V. Shuvaev, Vladimir R. Muzykantov, Servio H. Ramirez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8c574c0d411e41d5b652a7758170ba4f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8c574c0d411e41d5b652a7758170ba4f
record_format	dspace
spelling	oai:doaj.org-article:8c574c0d411e41d5b652a7758170ba4f2021-12-02T15:05:24ZAcute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury10.1038/s41598-017-03309-42045-2322https://doaj.org/article/8c574c0d411e41d5b652a7758170ba4f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03309-4https://doaj.org/toc/2045-2322Abstract 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.Evan M. LuttonRoshanak RazmpourAllison M. AndrewsLee Anne CannellaYoung-Jin SonVladimir V. ShuvaevVladimir R. MuzykantovServio H. RamirezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Evan M. Lutton Roshanak Razmpour Allison M. Andrews Lee Anne Cannella Young-Jin Son Vladimir V. Shuvaev Vladimir R. Muzykantov Servio H. Ramirez
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 Portfolio
publishDate	2017
url	https://doaj.org/article/8c574c0d411e41d5b652a7758170ba4f
work_keys_str_mv	AT evanmlutton acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury AT roshanakrazmpour acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury AT allisonmandrews acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury AT leeannecannella acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury AT youngjinson acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury AT vladimirvshuvaev acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury AT vladimirrmuzykantov acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury AT serviohramirez acuteadministrationofcatalasetargetedtoicam1attenuatesneuropathologyinexperimentaltraumaticbraininjury
_version_	1718388845243793408

Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury

Ejemplares similares