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L-PGDS Mediates Vagus Nerve Stimulation-Induced Neuroprotection in a Rat Model of Ischemic Stroke by Suppressing the Apoptotic Response

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Abstract

The role of lipocalin prostaglandin D2 synthase (L-PGDS) in brain ischemia has not been fully clarified to date. Vagus nerve stimulation (VNS) protects against cerebral ischemia/reperfusion (I/R) injury, but the mechanisms involved need further exploration. This study investigated the role of L-PGDS in cerebral I/R and whether this process was involved in the mechanism of VNS-mediated neuroprotection. Male Sprague–Dawley rats were pretreated with a lentiviral vector (LV) through intracerebroventricular injection, followed by middle cerebral artery occlusion (MCAO) and VNS treatment. The expression of L-PGDS in the peri-infarct cortex was examined. The localization of L-PGDS was determined using double immunofluorescence staining. Neurologic scores, infarct volume and neuronal apoptosis were evaluated at 24 h after reperfusion. The expression of apoptosis-related molecules was measured by western blot analysis. The expression of L-PGDS in the peri-infarct cortex increased at 12 h, reached a peak at 24 h after reperfusion, and lasted up to 3 days. VNS treatment further enhanced the expression of L-PGDS following ischemic stroke. L-PGDS was mainly expressed in neurons in the peri-infarct cortex. I/R rats treated with VNS showed better neurological deficit scores, reduced infarct volume, and decreased neuronal apoptosis as indicated by the decreased levels of Bax and cleaved caspase-3 as well as increased levels of Bcl-2. Strikingly, the beneficial effects of VNS were weakened after L-PGDS down-regulation. In general, our results suggest that L-PGDS is a potential mediator of VNS-induced neuroprotection against I/R injury.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (Grant No. 81271306).

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Authors and Affiliations

  1. Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, #76 Linjiang Road, Yuzhong District, Chongqing, 400010, China

    Lina Zhang, Jingxi Ma, Xinhao Jin, Gongwei Jia & Changqing Li

  2. Department of Neurology, Center for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, #6 Tian Tan Xi Li Street, Beijing, 100050, China

    Ying Jiang

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  1. Lina Zhang
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  2. Jingxi Ma
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  3. Xinhao Jin
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Correspondence to Changqing Li.

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Zhang, L., Ma, J., Jin, X. et al. L-PGDS Mediates Vagus Nerve Stimulation-Induced Neuroprotection in a Rat Model of Ischemic Stroke by Suppressing the Apoptotic Response. Neurochem Res 42, 644–655 (2017). https://doi.org/10.1007/s11064-016-2121-8

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