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Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model
Perinatal hypoxic ischemic encephalopathy (HIE) remains a major contributor of infant death and long-term disability worldwide. The role played by the complement system in this ischemia-reperfusion injury remains poorly understood. In order to better understand the role of complement activation and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483388/ https://www.ncbi.nlm.nih.gov/pubmed/34591905 http://dx.doi.org/10.1371/journal.pone.0257960 |
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author | Kumar, Parvathi Hair, Pamela Cunnion, Kenji Krishna, Neel Bass, Thomas |
author_facet | Kumar, Parvathi Hair, Pamela Cunnion, Kenji Krishna, Neel Bass, Thomas |
author_sort | Kumar, Parvathi |
collection | PubMed |
description | Perinatal hypoxic ischemic encephalopathy (HIE) remains a major contributor of infant death and long-term disability worldwide. The role played by the complement system in this ischemia-reperfusion injury remains poorly understood. In order to better understand the role of complement activation and other modifiable mechanisms of injury in HIE, we tested the dual-targeting anti-inflammatory peptide, RLS-0071 in an animal model of HIE. Using the well-established HIE rat pup model we measured the effects of RLS-0071 during the acute stages of the brain injury and on long-term neurocognitive outcomes. Rat pups subject to hypoxia-ischemia insult received one of 4 interventions including normothermia, hypothermia and RLS-0071 with and without hypothermia. We measured histopathological effects, brain C1q levels and neuroimaging at day 1 and 21 after the injury. A subset of animals was followed into adolescence and evaluated for neurocognitive function. On histological evaluation, RLS-0071 showed neuronal protection in combination with hypothermia (P = 0.048) in addition to reducing C1q levels in the brain at 1hr (P = 0.01) and at 8 hr in combination with hypothermia (P = 0.005). MRI neuroimaging demonstrated that RLS-0071 in combination with hypothermia reduced lesion volume at 24 hours (P<0.05) as well as decreased T2 signal at day 21 in combination with hypothermia (P<0.01). RLS-0071 alone or in combination with hypothermia improved both short-term and long-term memory. These findings suggest that modulation by RLS-0071 can potentially decrease brain damage resulting from HIE. |
format | Online Article Text |
id | pubmed-8483388 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-84833882021-10-01 Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model Kumar, Parvathi Hair, Pamela Cunnion, Kenji Krishna, Neel Bass, Thomas PLoS One Research Article Perinatal hypoxic ischemic encephalopathy (HIE) remains a major contributor of infant death and long-term disability worldwide. The role played by the complement system in this ischemia-reperfusion injury remains poorly understood. In order to better understand the role of complement activation and other modifiable mechanisms of injury in HIE, we tested the dual-targeting anti-inflammatory peptide, RLS-0071 in an animal model of HIE. Using the well-established HIE rat pup model we measured the effects of RLS-0071 during the acute stages of the brain injury and on long-term neurocognitive outcomes. Rat pups subject to hypoxia-ischemia insult received one of 4 interventions including normothermia, hypothermia and RLS-0071 with and without hypothermia. We measured histopathological effects, brain C1q levels and neuroimaging at day 1 and 21 after the injury. A subset of animals was followed into adolescence and evaluated for neurocognitive function. On histological evaluation, RLS-0071 showed neuronal protection in combination with hypothermia (P = 0.048) in addition to reducing C1q levels in the brain at 1hr (P = 0.01) and at 8 hr in combination with hypothermia (P = 0.005). MRI neuroimaging demonstrated that RLS-0071 in combination with hypothermia reduced lesion volume at 24 hours (P<0.05) as well as decreased T2 signal at day 21 in combination with hypothermia (P<0.01). RLS-0071 alone or in combination with hypothermia improved both short-term and long-term memory. These findings suggest that modulation by RLS-0071 can potentially decrease brain damage resulting from HIE. Public Library of Science 2021-09-30 /pmc/articles/PMC8483388/ /pubmed/34591905 http://dx.doi.org/10.1371/journal.pone.0257960 Text en © 2021 Kumar et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kumar, Parvathi Hair, Pamela Cunnion, Kenji Krishna, Neel Bass, Thomas Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model |
title | Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model |
title_full | Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model |
title_fullStr | Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model |
title_full_unstemmed | Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model |
title_short | Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model |
title_sort | classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483388/ https://www.ncbi.nlm.nih.gov/pubmed/34591905 http://dx.doi.org/10.1371/journal.pone.0257960 |
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