Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage
Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treat...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2014/495817 |
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| author | Melanie D. King Wittstatt A. Whitaker-Lea James M. Campbell Cargill H. Alleyne Krishnan M. Dhandapani |
| author_facet | Melanie D. King Wittstatt A. Whitaker-Lea James M. Campbell Cargill H. Alleyne Krishnan M. Dhandapani |
| author_sort | Melanie D. King |
| collection | DOAJ |
| description | Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH. |
| format | Article |
| id | doaj-art-02dc788543ab4e2bb84d2871f755d444 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-02dc788543ab4e2bb84d2871f755d4442025-02-03T05:58:39ZengWileyInternational Journal of Cell Biology1687-88761687-88842014-01-01201410.1155/2014/495817495817Necrostatin-1 Reduces Neurovascular Injury after Intracerebral HemorrhageMelanie D. King0Wittstatt A. Whitaker-Lea1James M. Campbell2Cargill H. Alleyne3Krishnan M. Dhandapani4Department of Neurosurgery, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USADepartment of Neurosurgery, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USADepartment of Neurosurgery, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USADepartment of Neurosurgery, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USADepartment of Neurosurgery, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USAIntracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.http://dx.doi.org/10.1155/2014/495817 |
| spellingShingle | Melanie D. King Wittstatt A. Whitaker-Lea James M. Campbell Cargill H. Alleyne Krishnan M. Dhandapani Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage International Journal of Cell Biology |
| title | Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage |
| title_full | Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage |
| title_fullStr | Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage |
| title_full_unstemmed | Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage |
| title_short | Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage |
| title_sort | necrostatin 1 reduces neurovascular injury after intracerebral hemorrhage |
| url | http://dx.doi.org/10.1155/2014/495817 |
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