Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage
Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive. The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH. The aim of the present...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2020-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=7;spage=1283;epage=1289;aulast=Ke |
| _version_ | 1819106746452410368 |
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| author | Da-Qiang Ke Zhi-Yang Chen Zhou-Ling Li Xia Huang Hui Liang |
| author_facet | Da-Qiang Ke Zhi-Yang Chen Zhou-Ling Li Xia Huang Hui Liang |
| author_sort | Da-Qiang Ke |
| collection | DOAJ |
| description | Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive. The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH. The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms. In this study, a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats. Z-IETD-FMK (0.5, 1, 2 mg/kg; an inhibitor of caspase-8) was delivered via intravenous (tail vein) injection immediately after subarachnoid hemorrhage. After 12 hours of subarachnoid hemorrhage, western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours, peaked at 24 hours, and then decreased at 72 hours after subarachnoid hemorrhage. Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage. Z-IETD-FMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage. The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21–27 days after subarachnoid hemorrhage. Furthermore, inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3, caspase-1, and interleukin-1β after subarachnoid hemorrhage. In conclusion, our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University, China (approval No. 2016-193) on February 25, 2016. |
| first_indexed | 2024-12-22T02:43:02Z |
| format | Article |
| id | doaj.art-22141d8469b4442a8ddf2e3d65cf7644 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-22T02:43:02Z |
| publishDate | 2020-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-22141d8469b4442a8ddf2e3d65cf76442022-12-21T18:41:36ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742020-01-011571283128910.4103/1673-5374.272613Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhageDa-Qiang KeZhi-Yang ChenZhou-Ling LiXia HuangHui LiangCaspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive. The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH. The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms. In this study, a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats. Z-IETD-FMK (0.5, 1, 2 mg/kg; an inhibitor of caspase-8) was delivered via intravenous (tail vein) injection immediately after subarachnoid hemorrhage. After 12 hours of subarachnoid hemorrhage, western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours, peaked at 24 hours, and then decreased at 72 hours after subarachnoid hemorrhage. Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage. Z-IETD-FMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage. The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21–27 days after subarachnoid hemorrhage. Furthermore, inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3, caspase-1, and interleukin-1β after subarachnoid hemorrhage. In conclusion, our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University, China (approval No. 2016-193) on February 25, 2016.http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=7;spage=1283;epage=1289;aulast=Kebrain water content; caspase-8; inflammation; morris water maze; neurological function; neuroprotection; pyrin domain-containing 3; rotarod test; subarachnoid hemorrhage; z-ietd-fmk |
| spellingShingle | Da-Qiang Ke Zhi-Yang Chen Zhou-Ling Li Xia Huang Hui Liang Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage Neural Regeneration Research brain water content; caspase-8; inflammation; morris water maze; neurological function; neuroprotection; pyrin domain-containing 3; rotarod test; subarachnoid hemorrhage; z-ietd-fmk |
| title | Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage |
| title_full | Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage |
| title_fullStr | Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage |
| title_full_unstemmed | Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage |
| title_short | Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage |
| title_sort | target inhibition of caspase 8 alleviates brain damage after subarachnoid hemorrhage |
| topic | brain water content; caspase-8; inflammation; morris water maze; neurological function; neuroprotection; pyrin domain-containing 3; rotarod test; subarachnoid hemorrhage; z-ietd-fmk |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=7;spage=1283;epage=1289;aulast=Ke |
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