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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0257960 |
| _version_ | 1818990347193155584 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T19:52:55Z |
| format | Article |
| id | doaj.art-632e0da05f98427c83b68800875cdff9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T19:52:55Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-632e0da05f98427c83b68800875cdff92022-12-21T19:28:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01169e025796010.1371/journal.pone.0257960Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model.Parvathi KumarPamela HairKenji CunnionNeel KrishnaThomas BassPerinatal 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.https://doi.org/10.1371/journal.pone.0257960 |
| spellingShingle | Parvathi Kumar Pamela Hair Kenji Cunnion Neel Krishna Thomas Bass Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0257960 |
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