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.

Effect of Visible Light on Vasospasticity of Post–Subarachnoid Hemorrhage Cerebrospinal Fluid

“…Since cerebral vasospasm (CV) was first recognized in 1951, many different theories have been proposed to explain its pathophysiology. [1][2][3][4][5] Some of these theories were negated in both clinical and experimental studies; the remainder failed to succeed clinically despite showing promising results in experimental studies. 6,7 Nitric oxide (NO) is made by the endothelial nitric oxide synthase (eNOS) in the intima and by the neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels.…”

Intracerebral Hemorrhage of Brainstem in triple pregnancy after in vitro fertilization by receiving Ovum Donation: A case report and review

“…Moreover, progesterone could reduce apoptosis in hippocampus and cortex; the hematoma volume, cerebral edema and proin lammatory recruitment. Progesterone seems to have bene icial effects on neurobehavioral recovery and modulate neuro-in lammation [22][23][24][25].…”

Sex-Specific Effects of Progesterone on Early Outcome of Intracerebral Hemorrhage

“…Similarly, progesterone promoted functional recovery in ischemic brain injury models [31,32,33,73,74] by reducing proinflammatory cytokine formation, decreasing infarct volume, minimizing hemorrhagic transformation, and maintaining blood-brain barrier integrity [23,24,25,26,27,28,29,30]. In SAH, progesterone attenuated vasospasm, reduced lipid peroxidation, and prevented apoptosis [35,36,37,38]. While mechanically different, ICH shares some similarities with trauma, ischemia, and SAH in pathophysiology, particularly in secondary neuroinflammation.…”

“…In ischemic stroke, progesterone reduced infarction size [23,24], suppressed neuroinflammation [25,26,27], minimized hemorrhagic transformation [28,29], decreased blood-brain barrier permeability [30], and improved outcome [31,32,33,34]. Progesterone showed similar beneficial effects in a rat model of subarachnoid hemorrhage (SAH) through attenuating vasospasm [35], preventing apoptosis [36], and reducing oxidative stress [37,38]. Progesterone also improved functional recovery in other neuroinflammatory diseases, including demyelinating diseases [39,40] and diabetic neuropathy [41].…”