title: L-PGDS Mediates Vagus Nerve Stimulation-Induced Neuroprotection in a Rat Model of Ischemic Stroke by Suppressing the Apoptotic Response.
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.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, #76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, #76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
authors.forename: Jingxi
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, #76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
authors.forename: Xinhao
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, #76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
authors.forename: Gongwei
authors.initials: G
authors.lastname: Jia
authors.affiliation: Department of Neurology, Center for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, #6 Tian Tan Xi Li Street, Beijing, 100050, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, #76 Linjiang Road, Yuzhong District, Chongqing, 400010, China. changqingli666@163.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D004195:Disease Models, Animal; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000627:therapeutic use; D054834:Lipocalins / Q000096:biosynthesis* / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism* / Q000517:prevention & control; D055536:Vagus Nerve Stimulation / Q000379:methods
chemical_list: D054834:Lipocalins; D018696:Neuroprotective Agents; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: Apoptosis; Cerebral ischemic and reperfusion; L-PGDS; Vagus nerve stimulation