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: Chia-Mao Chang, Yu-Feng Su, Chih-Zen Chang, Chia-Li Chung, Yee-Jean Tsai, Joon-Khim Loh, Chih-Lung Lin
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 207616 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 24949428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Progesterone
• Nitric Oxide Synthase
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Female
• Gene Expression Regulation
• Nitric Oxide Synthase (biosynthesis)
• Progesterone (administration & dosage)
• Proto-Oncogene Proteins c-akt (biosynthesis)
• Rats
• Signal Transduction (genetics)
• Subarachnoid Hemorrhage (drug therapy, metabolism, pathology)
• Transcriptional Activation (drug effects)
• Vasoconstriction (drug effects)
• Vasospasm, Intracranial (drug therapy, etiology, pathology)