Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats
Abstract Pre‐stroke exercise conditioning reduces neurovascular injury and improves functional outcomes after stroke. The goal of this study was to explore if post‐stroke exercise conditioning (PostE) reduced brain injury and whether it was associated with the regulation of gluconeogenesis. Adult ra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Brain and Behavior |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/brb3.2805 |
| _version_ | 1797893691714568192 |
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| author | Fengwu Li Xiaokun Geng Roxanne Ilagan Shangying Bai Yuhua Chen Yuchuan Ding |
| author_facet | Fengwu Li Xiaokun Geng Roxanne Ilagan Shangying Bai Yuhua Chen Yuchuan Ding |
| author_sort | Fengwu Li |
| collection | DOAJ |
| description | Abstract Pre‐stroke exercise conditioning reduces neurovascular injury and improves functional outcomes after stroke. The goal of this study was to explore if post‐stroke exercise conditioning (PostE) reduced brain injury and whether it was associated with the regulation of gluconeogenesis. Adult rats received 2 h of middle cerebral artery (MCA) occlusion, followed by 24 h of reperfusion. Treadmill activity was then initiated 24 h after reperfusion for PostE. The severity of the brain damage was determined by infarct volume, apoptotic cell death, and neurological deficit at one and three days after reperfusion. We measured gluconeogenesis including oxaloacetate (OAA), phosphoenolpyruvate (PEP), pyruvic acid, lactate, ROS, and glucose via ELISA, as well as the location and expression of the key enzyme phosphoenolpyruvate carboxykinase (PCK)‐1/2 via immunofluorescence. We also determined upstream pathways including forkhead transcription factor (FoxO1), p‐FoxO1, 3‐kinase (PI3K)/Akt, and p‐PI3K/Akt via Western blot. Additionally, the cytoplasmic expression of p‐FoxO1 was detected by immunofluorescence. Compared to non‐exercise control, PostE (*p < .05) decreased brain infarct volumes, neurological deficits, and cell death at one and three days. PostE groups (*p < .05) saw increases in OAA and decreases in PEP, pyruvic acid, lactate, ROS, glucose levels, and tissue PCKs expression on both days. PCK‐1/2 expressions were also significantly (*p < .05) suppressed by the exercise setting. Additionally, phosphorylated PI3K, AKT, and FoxO1 protein expression were significantly induced by PostE at one and three days (*p < .05). In this study, PostE reduced brain injury after stroke, in association with activated PI3K/AKT/FoxO1 signaling, and inhibited gluconeogenesis. These results suggest the involvement of FoxO1 regulation of gluconeogenesis underlying post‐stroke neuroprotection. |
| first_indexed | 2024-04-10T06:56:55Z |
| format | Article |
| id | doaj.art-394f46b1dd0f4f658051d90895ddb6ff |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-04-10T06:56:55Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-394f46b1dd0f4f658051d90895ddb6ff2023-02-28T07:01:06ZengWileyBrain and Behavior2162-32792023-01-01131n/an/a10.1002/brb3.2805Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in ratsFengwu Li0Xiaokun Geng1Roxanne Ilagan2Shangying Bai3Yuhua Chen4Yuchuan Ding5China‐America Institute of Neuroscience Beijing Luhe Hospital, Capital Medical University Beijing ChinaChina‐America Institute of Neuroscience Beijing Luhe Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Wayne State University School of Medicine Detroit Michigan USAChina‐America Institute of Neuroscience Beijing Luhe Hospital, Capital Medical University Beijing ChinaDepartment of Developmental Cell Biology Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University Shenyang ChinaDepartment of Neurosurgery Wayne State University School of Medicine Detroit Michigan USAAbstract Pre‐stroke exercise conditioning reduces neurovascular injury and improves functional outcomes after stroke. The goal of this study was to explore if post‐stroke exercise conditioning (PostE) reduced brain injury and whether it was associated with the regulation of gluconeogenesis. Adult rats received 2 h of middle cerebral artery (MCA) occlusion, followed by 24 h of reperfusion. Treadmill activity was then initiated 24 h after reperfusion for PostE. The severity of the brain damage was determined by infarct volume, apoptotic cell death, and neurological deficit at one and three days after reperfusion. We measured gluconeogenesis including oxaloacetate (OAA), phosphoenolpyruvate (PEP), pyruvic acid, lactate, ROS, and glucose via ELISA, as well as the location and expression of the key enzyme phosphoenolpyruvate carboxykinase (PCK)‐1/2 via immunofluorescence. We also determined upstream pathways including forkhead transcription factor (FoxO1), p‐FoxO1, 3‐kinase (PI3K)/Akt, and p‐PI3K/Akt via Western blot. Additionally, the cytoplasmic expression of p‐FoxO1 was detected by immunofluorescence. Compared to non‐exercise control, PostE (*p < .05) decreased brain infarct volumes, neurological deficits, and cell death at one and three days. PostE groups (*p < .05) saw increases in OAA and decreases in PEP, pyruvic acid, lactate, ROS, glucose levels, and tissue PCKs expression on both days. PCK‐1/2 expressions were also significantly (*p < .05) suppressed by the exercise setting. Additionally, phosphorylated PI3K, AKT, and FoxO1 protein expression were significantly induced by PostE at one and three days (*p < .05). In this study, PostE reduced brain injury after stroke, in association with activated PI3K/AKT/FoxO1 signaling, and inhibited gluconeogenesis. These results suggest the involvement of FoxO1 regulation of gluconeogenesis underlying post‐stroke neuroprotection.https://doi.org/10.1002/brb3.2805conditioninggluconeogenesisneuroprotectionPI3K/AKT/FoxO1rehabilitation |
| spellingShingle | Fengwu Li Xiaokun Geng Roxanne Ilagan Shangying Bai Yuhua Chen Yuchuan Ding Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats Brain and Behavior conditioning gluconeogenesis neuroprotection PI3K/AKT/FoxO1 rehabilitation |
| title | Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats |
| title_full | Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats |
| title_fullStr | Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats |
| title_full_unstemmed | Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats |
| title_short | Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats |
| title_sort | exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats |
| topic | conditioning gluconeogenesis neuroprotection PI3K/AKT/FoxO1 rehabilitation |
| url | https://doi.org/10.1002/brb3.2805 |
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