Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia
(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic...
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MDPI AG
2022-06-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/12/3343 |
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| author | Sarah Gelhard Roxane-Isabelle Kestner Moritz Armbrust Helmuth Steinmetz Christian Foerch Ferdinand O. Bohmann |
| author_facet | Sarah Gelhard Roxane-Isabelle Kestner Moritz Armbrust Helmuth Steinmetz Christian Foerch Ferdinand O. Bohmann |
| author_sort | Sarah Gelhard |
| collection | DOAJ |
| description | (1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, <i>p</i> = 0.02; at 14 days, <i>p</i> = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (<i>p</i> = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role. |
| first_indexed | 2024-03-09T23:28:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T23:28:09Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-4abd11c6cb38403f87ae096dd429c9922023-11-23T17:14:37ZengMDPI AGJournal of Clinical Medicine2077-03832022-06-011112334310.3390/jcm11123343Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and HyperglycemiaSarah Gelhard0Roxane-Isabelle Kestner1Moritz Armbrust2Helmuth Steinmetz3Christian Foerch4Ferdinand O. Bohmann5Department of Neurology, Goethe University, Schleusenweg 2-16, 60528 Frankfurt am Main, GermanyDepartment of Neurology, Goethe University, Schleusenweg 2-16, 60528 Frankfurt am Main, GermanyInstitute of Neurology (Edinger Institute), Goethe University, 60528 Frankfurt am Main, GermanyDepartment of Neurology, Goethe University, Schleusenweg 2-16, 60528 Frankfurt am Main, GermanyDepartment of Neurology, Goethe University, Schleusenweg 2-16, 60528 Frankfurt am Main, GermanyDepartment of Neurology, Goethe University, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, <i>p</i> = 0.02; at 14 days, <i>p</i> = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (<i>p</i> = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.https://www.mdpi.com/2077-0383/11/12/3343strokethrombolysishemorrhagic transformationhyperglycemia |
| spellingShingle | Sarah Gelhard Roxane-Isabelle Kestner Moritz Armbrust Helmuth Steinmetz Christian Foerch Ferdinand O. Bohmann Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia Journal of Clinical Medicine stroke thrombolysis hemorrhagic transformation hyperglycemia |
| title | Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia |
| title_full | Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia |
| title_fullStr | Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia |
| title_full_unstemmed | Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia |
| title_short | Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia |
| title_sort | exploring contraindications for thrombolysis risk of hemorrhagic transformation and neurological deterioration after thrombolysis in mice with recent ischemic stroke and hyperglycemia |
| topic | stroke thrombolysis hemorrhagic transformation hyperglycemia |
| url | https://www.mdpi.com/2077-0383/11/12/3343 |
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