Axon Guidance and Neuronal Signaling
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Abstract
Abstract
Diabetes Mellitus (DM) is a major comorbidity that exacerbates ischemic brain injury and hinders functional recovery following stroke. Given that angiogenesis and the maintenance of blood-brain barrier (BBB) integrity are essential for neurorestoration, understanding how DM influences these processes and the molecular mechanisms involved is critical for improving clinical outcomes. To investigate these effects, a type 1 DM model was established in six-week-old mice via intraperitoneal injections of streptozotocin (60 mg/kg/day for 5 days), with success confirmed by blood glucose testing two weeks later. Focal ischemic stroke was subsequently induced using a photothrombosis model. Functional recovery was assessed using neurological scoring, the Rotarod test, and the foot-fault test. Post-stroke neovascularization was quantified via lectin injection, while BBB integrity was evaluated through IgG leakage, pericyte coverage, and the expression of tight junction proteins (Zo-1, occludin, and claudin-5). Additionally, protein expression within the Slit2/Robo/CRTC1 pathway was analyzed 1, 7, and 14 days post-stroke using immunofluorescence and western blotting. Our results demonstrated that DM significantly impaired sensorimotor recovery and hindered reparative neovascularization in the peri-infarct area. Furthermore, DM exacerbated BBB disruption, as evidenced by increased IgG leakage, reduced expression of occludin and claudin-5, and diminished pericyte coverage. Mechanistically, DM led to a decrease in Robo1 and an increase in Robo4 expression without altering Slit2 levels. Additionally, DM further suppressed the expression of the co-transcription factor CRTC1 following the ischemic event. Our findings indicate that DM impairs post-stroke angiogenesis and BBB repair accompanied by the dysregulation of the Slit2/Robo/CRTC1 signalling pathway. These results highlight a potential therapeutic target for enhancing stroke recovery in diabetic populations.
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@article{Wang2026Diabetes,
title = {Diabetes Impairs Post-stroke Angiogenesis and BBB Integrity Accompanied by Dysregulated Slit2/Robo-CRTC1 Pathway},
author = {Yanping Wang and Xuemei Shi and Xiaoyun Zhao and Xudong Lu and Jingxia Gu and Hui Guo and Yihui Wang and Xiaoqiang Wu and Congying Xu and Minghui Shen and Yufei Shen and Chun Guo and Yanan Hao and Shuxia Qian and Xinchun Jin},
journal = {Cellular and Molecular Neurobiology},
year = {2026},
doi = {10.1007/s10571-026-01811-w},
url = {https://doi.org/10.1007/s10571-026-01811-w}
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