ArticleStroke and vascular neurology2023
Oestrogen ameliorates blood-brain barrier damage after experimental subarachnoid haemorrhage via the SHH pathway in male rats.
Article in Stroke and vascular neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- A comprehensive meta-analysis of exogenous estrogen, progesterone, and testosterone in animal models of ischemic and hemorrhagic stroke.Biology of sex differences · 2026Pooled it
- Sestrin2 Mitigates Neuronal Ferroptosis Following Subarachnoid Hemorrhage via Orchestration of the AMPK/PGC1α/Nrf2 Signaling Axis.CNS neuroscience & therapeutics · 2026Article
- Hedgehog Signaling Functions in Spermatogenesis and Keeping Hemolymph-Testis Barrier Stability inInternational journal of molecular sciences · 2025Article
- Out of the core: the impact of focal ischemia in regions beyond the penumbra.Frontiers in cellular neuroscience · 2024Review
- Sex-dependent temporal changes in astrocyte-vessel interactions following diffuse traumatic brain injury in rats.Frontiers in physiology · 2024Article
- Clinical Potential of Immunotherapies in Subarachnoid Hemorrhage Treatment: Mechanistic Dissection of Innate and Adaptive Immune Responses.Aging and disease · 2023Review
- Ticagrelor plus aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis.BMC neurology · 2023Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSex differences affect the occurrence, progression and regression of subarachnoid haemorrhage (SAH). Oestrogen plays a protective role in alleviating the vasospasm and neuronal apoptosis induced by SAH. However, whether oestrogen affects blood‒brain barrier (BBB) integrity has not been fully studied. Oestrogen has been found to regulate the sonic hedgehog (SHH) signalling pathway through the oestrogen receptor in gastric cancer and adrenal glands, and the SHH signalling pathway has an important role in maintaining the BBB by upregulating the expression of tight junction proteins. In this study, we investigated the relationship between oestrogen and the SHH signalling pathway using clinical data and established an experimental SAH model to explore whether oestrogen could ameliorate BBB damage after SAH through the SHH pathway.
methodsCorrelations between oestrogen and the SHH pathway were analysed by patients' cerebrospinal fluid (CSF) samples and the Genotype-Tissue Expression database (GTEx). Then, an experimental rat SAH model was established using the endovascular perforation method and treated with oestrogen, oestrogen inhibitors and SHH signalling pathway inhibitors. Then, the effects of oestrogen on BBB damage were analysed by western blot, immunofluorescence and neurobehavioural experiments.
resultsESLIA detection and correlation analysis showed that oestrogen levels in patients' CSF were positively correlated with the SHH pathway, which was further verified by GTEx gene-correlation analysis. SHH was found to be mainly expressed in neurons and astrocytes in rats under physiological conditions and was upregulated by oestrogen pretreatment. In the SAH model, oestrogen pretreatment was found to reverse SAH-induced decreases in the SHH pathway, which were counteracted by oestrogen receptor inhibitors. Furthermore, oestrogen pretreatment reduced SAH-induced BBB damage, brain oedema and neurological dysfunction, which were eliminated by SHH pathway inhibitors.
conclusionIn conclusion, we demonstrate here that oestrogen pretreatment ameliorates brain injury after SAH, at least in part through SHH pathway-mediated BBB protection.
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