ArticleNeurosurgery2012
Phosphodiesterase 5 inhibition attenuates cerebral vasospasm and improves functional recovery after experimental subarachnoid hemorrhage.
Article in Neurosurgery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Glycogen Synthase Kinase-3β Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix-intraventricular Hemorrhage of the Preterm Newborn.Translational stroke research · 2025Article
- Subarachnoid Hemorrhage Induces Sub-acute and Early Chronic Impairment in Learning and Memory in Mice.Translational stroke research · 2022Article
- The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.Fluids and barriers of the CNS · 2022Review
- The Role of Sildenafil in Treating Brain Injuries in Adults and Neonates.Frontiers in cellular neuroscience · 2022Review
- Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia in Subarachnoid Hemorrhage in Response to Hypoxic Postconditioning.Journal of the American Heart Association · 2021Article
- NLRP3 inhibition attenuates early brain injury and delayed cerebral vasospasm after subarachnoid hemorrhage.Journal of neuroinflammation · 2021Article
- Anesthetic and subanesthetic doses of isoflurane conditioning provides strong protection against delayed cerebral ischemia in a mouse model of subarachnoid hemorrhage.Brain research · 2021Article
- SIRT1 mediates hypoxic preconditioning induced attenuation of neurovascular dysfunction following subarachnoid hemorrhage.Experimental neurology · 2020Article
- Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Neuroinflammation and Microvascular Dysfunction After Experimental Subarachnoid Hemorrhage: Emerging Components of Early Brain Injury Related to Outcome.Neurocritical care · 2019Review
- Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score.Journal of the American Heart Association · 2019Article
- Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage.Translational stroke research · 2018Article
- Minocycline protects against delayed cerebral ischemia after subarachnoid hemorrhage via matrix metalloproteinase-9 inhibition.Annals of clinical and translational neurology · 2017Article
- Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Review
- A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage.Scientific reports · 2017Article
- Minimal Long-Term Neurobehavioral Impairments after Endovascular Perforation Subarachnoid Hemorrhage in Mice.Scientific reports · 2017Article
- Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage.Neurocritical care · 2016Article
- Intracranial aneurysm and sildenafil.Proceedings (Baylor University. Medical Center) · 2016Article
- A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage.Journal of neurosurgery · 2016Article
- Phosphodiesterase inhibitors as therapeutics for traumatic brain injury.Current pharmaceutical design · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCerebral vasospasm is an independent predictor of poor outcome after subarachnoid hemorrhage (SAH). The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) vasodilatory pathway is strongly implicated in its pathophysiology. Preliminary studies suggest that phosphodiesterase 5 (PDE5), an enzyme that degrades cGMP, may play a role because the PDE5 inhibitor sildenafil was found to reduce vasospasm after SAH. However, several questions that are critical when considering translational studies remain unanswered.
objectiveTo elucidate the mechanism of action of sildenafil against vasospasm and to assess whether sildenafil attenuates SAH-induced neuronal cell death, improves functional outcome after SAH, or causes significant physiological side effects when administered at therapeutically relevant doses.
methodsSAH was induced via endovascular perforation in male C57BL6 mice. Beginning 2 hours later, mice received sildenafil citrate (0.7, 2 or 5 mg/kg orally twice daily) or vehicle. Neurological outcome was assessed daily. Vasospasm was determined on post-SAH day 3. Brain PDE5 expression and activity, cGMP content, neuronal cell death, arterial blood pressure, and intracranial pressure were examined.
resultsWe found that PDE5 activity (but not expression) is increased after SAH, leading to decreased cGMP levels. Sildenafil attenuates this increase in PDE5 activity and restores cGMP levels after SAH. Post-SAH initiation of sildenafil was found to decrease vasospasm and neuronal cell death and markedly improve neurological outcome without causing significant physiological side effects.
conclusionSildenafil, a US Food and Drug Administration-approved drug with a proven track record of safety in humans, is a promising new therapy for vasospasm and neurological deficits after SAH.
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Registered trials
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