Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat.
After intracerebral hemorrhage (ICH), brain edema commonly occurs and can cause death. Along with edema, there are significant alterations in the concentrations of key ions such as sodium, potassium, and chloride, which are essential to brain function. NKCC1, a cation-chloride cotransporter, is upre...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0210660 |
| _version_ | 1818916398160674816 |
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| author | Cassandra M Wilkinson Brittany A Fedor Jasmine R Aziz Colby A Nadeau Paul S Brar Julia J A Clark Frederick Colbourne |
| author_facet | Cassandra M Wilkinson Brittany A Fedor Jasmine R Aziz Colby A Nadeau Paul S Brar Julia J A Clark Frederick Colbourne |
| author_sort | Cassandra M Wilkinson |
| collection | DOAJ |
| description | After intracerebral hemorrhage (ICH), brain edema commonly occurs and can cause death. Along with edema, there are significant alterations in the concentrations of key ions such as sodium, potassium, and chloride, which are essential to brain function. NKCC1, a cation-chloride cotransporter, is upregulated after brain damage, such as traumatic injury and ischemic stroke. NKCC1 brings sodium and chloride into the cell, possibly worsening ion dyshomeostasis. Bumetanide, a specific NKCC1 antagonist, blocks the transport of chloride into cells, and thus should attenuate the increases in chloride, which should lessen brain edema and improve neuronal functioning post-ICH, as with other injuries. We used the collagenase model of ICH to test whether bumetanide treatment for three days (vs. vehicle) would improve outcome. We gave bumetanide beginning at two hours or seven days post-ICH and measured behavioural outcome, edema, and brain ion content after treatment. There was some evidence for a minor reduction in edema after early dosing, but this did not improve behaviour or lessen injury. Contrary to our hypothesis, bumetanide did not normalize ion concentrations after late dosing. Bumetanide did not improve behavioural outcome or affect lesion volume. After ICH, bumetanide is safe to use in rats but does not improve functional outcome in the majority of animals. |
| first_indexed | 2024-12-20T00:17:32Z |
| format | Article |
| id | doaj.art-08de905618234beb9e0ffc55ca3cecd2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T00:17:32Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-08de905618234beb9e0ffc55ca3cecd22022-12-21T20:00:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01141e021066010.1371/journal.pone.0210660Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat.Cassandra M WilkinsonBrittany A FedorJasmine R AzizColby A NadeauPaul S BrarJulia J A ClarkFrederick ColbourneAfter intracerebral hemorrhage (ICH), brain edema commonly occurs and can cause death. Along with edema, there are significant alterations in the concentrations of key ions such as sodium, potassium, and chloride, which are essential to brain function. NKCC1, a cation-chloride cotransporter, is upregulated after brain damage, such as traumatic injury and ischemic stroke. NKCC1 brings sodium and chloride into the cell, possibly worsening ion dyshomeostasis. Bumetanide, a specific NKCC1 antagonist, blocks the transport of chloride into cells, and thus should attenuate the increases in chloride, which should lessen brain edema and improve neuronal functioning post-ICH, as with other injuries. We used the collagenase model of ICH to test whether bumetanide treatment for three days (vs. vehicle) would improve outcome. We gave bumetanide beginning at two hours or seven days post-ICH and measured behavioural outcome, edema, and brain ion content after treatment. There was some evidence for a minor reduction in edema after early dosing, but this did not improve behaviour or lessen injury. Contrary to our hypothesis, bumetanide did not normalize ion concentrations after late dosing. Bumetanide did not improve behavioural outcome or affect lesion volume. After ICH, bumetanide is safe to use in rats but does not improve functional outcome in the majority of animals.https://doi.org/10.1371/journal.pone.0210660 |
| spellingShingle | Cassandra M Wilkinson Brittany A Fedor Jasmine R Aziz Colby A Nadeau Paul S Brar Julia J A Clark Frederick Colbourne Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat. PLoS ONE |
| title | Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat. |
| title_full | Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat. |
| title_fullStr | Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat. |
| title_full_unstemmed | Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat. |
| title_short | Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat. |
| title_sort | failure of bumetanide to improve outcome after intracerebral hemorrhage in rat |
| url | https://doi.org/10.1371/journal.pone.0210660 |
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