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Immediate remote ischemic postconditioning reduces cerebral damage in ischemic stroke mice by enhancing leptomeningeal collateral circulation |
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| Authors: | Ying Zhang Longhui Ma Changhong Ren Kaiyin Liu Xin Tian Di Wu Yuchuan Ding Junfa Li Cesar V. Borlongan Xunming Ji |
| Affiliation: | 1. Department of Neurobiology, Capital Medical University, Beijing, China;2. Department of Neurobiology, Capital Medical University, Beijing, China Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China;3. Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China;4. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan;5. Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, Florida;6. Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China |
| Abstract: | Remote ischemic postconditioning (RIPC) is a promising neuroprotective strategy for ischemic stroke. Here, we employed a focal ischemic stroke mouse model to test the hypothesis that poststroke collateral circulation as a potent mechanism of action underlying the therapeutic effects of immediate RIPC. During reperfusion of cerebral ischemia, the mice were randomly assigned to receive RIPC, granulocyte colony-stimulating factor (G-CSF) as a positive control, or no treatment. At 24 hr, we found RIPC and G-CSF increased monocytes/macrophages in the dorsal brain surface and in the spleen, coupled with enhanced leptomeningeal collateral flow compared with nontreatment group. Blood monocytes depletion by 5-fluorouracil (5-FU) significantly limited the neuroprotection of RIPC or G-CSF treatment. The protein expression of proangiogenic factors such as Ang-2 was increased by ischemia, but treatment with either RIPC or G-CSF showed no further upregulation. Thus, immediate RIPC confers neuroprotection, in part, by enhancing leptomeningeal collateral circulation in a mouse model of ischemic stroke. |
| Keywords: | animal models collateral circulation ischemic stroke monocytes/macrophages remote ischemic postconditioning |