Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia
Hemorrhagic transformation (HT) has been reported to be associated with a poor prognosis after acute ischemic stroke. Blood-brain barrier (BBB) damage is considered as the major pathophysiologic mechanism of HT. Our aim was to investigate the role of acute iron overload in BBB damage and HT after tr...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | IBRO Neuroscience Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242122000458 |
| _version_ | 1828163096838930432 |
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| author | Qian Wu Chenchen Wei Siqi Guo Junfeng Liu Hengyi Xiao Simiao Wu Bo Wu Ming Liu |
| author_facet | Qian Wu Chenchen Wei Siqi Guo Junfeng Liu Hengyi Xiao Simiao Wu Bo Wu Ming Liu |
| author_sort | Qian Wu |
| collection | DOAJ |
| description | Hemorrhagic transformation (HT) has been reported to be associated with a poor prognosis after acute ischemic stroke. Blood-brain barrier (BBB) damage is considered as the major pathophysiologic mechanism of HT. Our aim was to investigate the role of acute iron overload in BBB damage and HT after transient focal ischemia in rats with hyperglycemia. Transient middle cerebral artery occlusion (MCAO) was induced in rats with hyperglycemia. Animals were assigned to four groups: Sham, Vehicle, Iron overload and Iron chelator treatment groups. Brain samples were collected at 24 h after surgery to quantify the amount of hemorrhage, determine extravasation of Evans blue and detect the levels of following proteins: ferritin, matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), Occludin and Claudin-5 by western blot analysis and immunohistochemistry. Compared to the Vehicle group, the Iron overload group had a significantly higher amount of hemorrhage and more extravasation of Evans blue. The Iron overload group had lower levels of ZO-1, Occludin and Claudin-5 and higher levels of ferritin and MMP-9 than the Vehicle group. Administering iron chelator reduced the extension of hemorrhage and extravasation of Evans blue, reversed the MCAO-induced reduction of ZO-1, Occludin and Claudin-5 and decreased the levels of ferritin and MMP-9. Our results suggest that acute iron overload aggravates BBB damage and HT after transient ischemia in rats with hyperglycemia, which provides basic evidence for iron overload as a potential factor associated with BBB damage and HT in ischemic stroke patients when accompanied with hyperglycemia. |
| first_indexed | 2024-04-12T01:05:37Z |
| format | Article |
| id | doaj.art-64844b0f7fb3485fa129291cf4013df1 |
| institution | Directory Open Access Journal |
| issn | 2667-2421 |
| language | English |
| last_indexed | 2024-04-12T01:05:37Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj.art-64844b0f7fb3485fa129291cf4013df12022-12-22T03:54:18ZengElsevierIBRO Neuroscience Reports2667-24212022-12-01138795Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemiaQian Wu0Chenchen Wei1Siqi Guo2Junfeng Liu3Hengyi Xiao4Simiao Wu5Bo Wu6Ming Liu7Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, ChinaDepartment of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaWest China School of Clinical Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, ChinaCenter of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, ChinaLab for Aging Research, Center for Medical Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, ChinaCenter of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, ChinaCenter of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, ChinaCenter of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Correspondence to: Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu 610041, Sichuan Province, China.Hemorrhagic transformation (HT) has been reported to be associated with a poor prognosis after acute ischemic stroke. Blood-brain barrier (BBB) damage is considered as the major pathophysiologic mechanism of HT. Our aim was to investigate the role of acute iron overload in BBB damage and HT after transient focal ischemia in rats with hyperglycemia. Transient middle cerebral artery occlusion (MCAO) was induced in rats with hyperglycemia. Animals were assigned to four groups: Sham, Vehicle, Iron overload and Iron chelator treatment groups. Brain samples were collected at 24 h after surgery to quantify the amount of hemorrhage, determine extravasation of Evans blue and detect the levels of following proteins: ferritin, matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), Occludin and Claudin-5 by western blot analysis and immunohistochemistry. Compared to the Vehicle group, the Iron overload group had a significantly higher amount of hemorrhage and more extravasation of Evans blue. The Iron overload group had lower levels of ZO-1, Occludin and Claudin-5 and higher levels of ferritin and MMP-9 than the Vehicle group. Administering iron chelator reduced the extension of hemorrhage and extravasation of Evans blue, reversed the MCAO-induced reduction of ZO-1, Occludin and Claudin-5 and decreased the levels of ferritin and MMP-9. Our results suggest that acute iron overload aggravates BBB damage and HT after transient ischemia in rats with hyperglycemia, which provides basic evidence for iron overload as a potential factor associated with BBB damage and HT in ischemic stroke patients when accompanied with hyperglycemia.http://www.sciencedirect.com/science/article/pii/S2667242122000458Iron overloadBlood-brain barrierHemorrhagic transformationIron chelatorFerritinMetalloproteinase-9 |
| spellingShingle | Qian Wu Chenchen Wei Siqi Guo Junfeng Liu Hengyi Xiao Simiao Wu Bo Wu Ming Liu Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia IBRO Neuroscience Reports Iron overload Blood-brain barrier Hemorrhagic transformation Iron chelator Ferritin Metalloproteinase-9 |
| title | Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia |
| title_full | Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia |
| title_fullStr | Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia |
| title_full_unstemmed | Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia |
| title_short | Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia |
| title_sort | acute iron overload aggravates blood brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia |
| topic | Iron overload Blood-brain barrier Hemorrhagic transformation Iron chelator Ferritin Metalloproteinase-9 |
| url | http://www.sciencedirect.com/science/article/pii/S2667242122000458 |
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