Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications
Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2016-01-01
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| Series: | Brain Circulation |
| Subjects: | |
| Online Access: | http://www.braincirculation.org/article.asp?issn=2394-8108;year=2016;volume=2;issue=1;spage=8;epage=19;aulast=Iqbal |
| _version_ | 1819262222383185920 |
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| author | Sana Iqbal Erik G Hayman Caron Hong Jesse A Stokum David B Kurland Volodymyr Gerzanich J Marc Simard |
| author_facet | Sana Iqbal Erik G Hayman Caron Hong Jesse A Stokum David B Kurland Volodymyr Gerzanich J Marc Simard |
| author_sort | Sana Iqbal |
| collection | DOAJ |
| description | Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH. |
| first_indexed | 2024-12-23T19:54:16Z |
| format | Article |
| id | doaj.art-8b62e0dd3077462ba5044b0a1b4e328a |
| institution | Directory Open Access Journal |
| issn | 2455-4626 |
| language | English |
| last_indexed | 2024-12-23T19:54:16Z |
| publishDate | 2016-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Brain Circulation |
| spelling | doaj.art-8b62e0dd3077462ba5044b0a1b4e328a2022-12-21T17:33:17ZengWolters Kluwer Medknow PublicationsBrain Circulation2455-46262016-01-012181910.4103/2394-8108.178541Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implicationsSana IqbalErik G HaymanCaron HongJesse A StokumDavid B KurlandVolodymyr GerzanichJ Marc SimardAneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.http://www.braincirculation.org/article.asp?issn=2394-8108;year=2016;volume=2;issue=1;spage=8;epage=19;aulast=IqbalHeparinnitric oxide (NO)NOS-1NOS-2NOS-3subarachnoid hemorrhage (SAH) |
| spellingShingle | Sana Iqbal Erik G Hayman Caron Hong Jesse A Stokum David B Kurland Volodymyr Gerzanich J Marc Simard Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications Brain Circulation Heparin nitric oxide (NO) NOS-1 NOS-2 NOS-3 subarachnoid hemorrhage (SAH) |
| title | Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications |
| title_full | Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications |
| title_fullStr | Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications |
| title_full_unstemmed | Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications |
| title_short | Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications |
| title_sort | inducible nitric oxide synthase nos 2 in subarachnoid hemorrhage regulatory mechanisms and therapeutic implications |
| topic | Heparin nitric oxide (NO) NOS-1 NOS-2 NOS-3 subarachnoid hemorrhage (SAH) |
| url | http://www.braincirculation.org/article.asp?issn=2394-8108;year=2016;volume=2;issue=1;spage=8;epage=19;aulast=Iqbal |
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