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...

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Autores principales:	Parvathi Kumar, Pamela Hair, Kenji Cunnion, Neel Krishna, Thomas Bass
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/632e0da05f98427c83b68800875cdff9
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spelling	oai:doaj.org-article:632e0da05f98427c83b68800875cdff92021-12-02T20:13:55ZClassical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model.1932-620310.1371/journal.pone.0257960https://doaj.org/article/632e0da05f98427c83b68800875cdff92021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257960https://doaj.org/toc/1932-6203Perinatal 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.Parvathi KumarPamela HairKenji CunnionNeel KrishnaThomas BassPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257960 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Parvathi Kumar Pamela Hair Kenji Cunnion Neel Krishna Thomas Bass Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model.
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	article
author	Parvathi Kumar Pamela Hair Kenji Cunnion Neel Krishna Thomas Bass
author_facet	Parvathi Kumar Pamela Hair Kenji Cunnion Neel Krishna Thomas Bass
author_sort	Parvathi Kumar
title	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_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_sort	classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/632e0da05f98427c83b68800875cdff9
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Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model.

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