title: Progesterone attenuates experimental subarachnoid hemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Akt signaling pathway.
abstract: Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still elusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone treatment significantly (P < 0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone might be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan ; Department of Surgery, Kaohsiung Municipal Hsiao Kang Hospital, No. 482, Shanming Road, Siaogang District, Kaohsiung 81267, Taiwan.
authors.forename: Chia-Mao
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan ; Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan ; Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung No. 68, Jhonghua 3rd Road, Cianjin District, Kaohsiung City 80145, Taiwan.
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan ; Department of Surgery, Kaohsiung Municipal Hsiao Kang Hospital, No. 482, Shanming Road, Siaogang District, Kaohsiung 81267, Taiwan.
authors.forename: Chia-Li
authors.identifier: 0000-0003-0224-479X
authors.initials: CL
authors.lastname: Chung
authors.affiliation: Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Yee-Jean
authors.initials: YJ
authors.lastname: Tsai
authors.affiliation: Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Joon-Khim
authors.initials: JK
authors.lastname: Loh
authors.affiliation: Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan ; Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Chih-Lung
authors.identifier: 0000-0002-6716-2771
authors.initials: CL
authors.lastname: Lin
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011374:Progesterone / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*
chemical_list: D011374:Progesterone; D019001:Nitric Oxide Synthase; D051057:Proto-Oncogene Proteins c-akt