ArticleInternational journal of molecular medicine2020
HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model.
Article in International journal of molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 42 citations in OpenAlex.
- Biomolecular Condensates Integrate Transcriptional and Epigenetic Responses to Hypoxia.International journal of molecular sciences · 2026Review
- Targeting ferroptosis and oxidative stress crosstalk: a new frontier in stroke neuroprotection.Journal of molecular histology · 2026Review
- Hypoxia-inducible factor-1α: Dual roles in maintaining neuronal homeostasis and neuronal degeneration via regulation of oxidative stress, mitochondrial dynamics, and bioenergetics.Journal of physiology and biochemistry · 2026Review
- Audiogenic Kindling Stimulation Fails to Induce Cerebral Overexpression of P-Glycoprotein and Limbic Crises in the GASH/Sal Model of Epilepsy.International journal of molecular sciences · 2026Article
- HIF-1α in ischemic stroke: context-dependent roles in ferroptosis and neurovascular repair.Frontiers in neurology · 2026Review
- Breaking the noninflamed barrier: tumor-secreted erythropoietin as a master regulator of immunosuppressive macrophages.Journal of the National Cancer Center · 2025Article
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Remote Ischemic Postconditioning Protects the Neurovascular Units in MCAO/R Rats through HIF-1α-Mediated Pathway.ACS omega · 2025Article
- Neuroprotective effects of arctigenin on cerebral ischemia-reperfusion injury in rats via the EPO/EPOR-JAK2-STAT5 signaling pathway.Frontiers in pharmacology · 2025Article
- Hypoxia-inducible Factor-1α Pathway in Cerebral Ischemia: From Molecular Mechanisms to Therapeutic Targets.CNS & neurological disorders drug targets · 2025Review
- Dim light at night shifts microglia to a pro-inflammatory state after cerebral ischemia, altering stroke outcome in mice.Experimental neurology · 2024Article
- Detrimental Roles of Hypoxia-Inducible Factor-1α in Severe Hypoxic Brain Diseases.International journal of molecular sciences · 2024Review
- Article
- HIF-1α promotes astrocytic production of macrophage migration inhibitory factor following spinal cord injury.CNS neuroscience & therapeutics · 2023Article
- Potential Role of Natural Antioxidants in Countering Reperfusion Injury in Acute Myocardial Infarction and Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2023Review
- A narrative review on treatment strategies for neonatal hypoxic ischemic encephalopathy.Translational pediatrics · 2023Review
- The Brain at High Altitude: From Molecular Signaling to Cognitive Performance.International journal of molecular sciences · 2023Review
- REST Targets JAK-STAT and HIF-1 Signaling Pathways in Human Down Syndrome Brain and Neural Cells.International journal of molecular sciences · 2023Article
- Recombinant Adenovirus-Mediated HIF-lα Ameliorates Neurological Dysfunction by Improving Energy Metabolism in Ischemic Penumbra After Cerebral Ischemia-Reperfusion in Rats.Neuropsychiatric disease and treatment · 2023Article
- Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia.Frontiers in pharmacology · 2023Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia‑inducible factor‑1α (HIF‑1α) is a key transcriptional factor in response to hypoxia and is involved in ischemic stroke. In the present study, the potential for HIF‑1α to inhibit neuronal apoptosis through upregulating erythropoietin (EPO) was investigated in a transient middle cerebral artery occlusion (tMCAO) rat stroke model. For this purpose, a recombinant adenovirus expressing HIF‑1α was engineered (Ad‑HIF‑1α). Control adenovirus (Ad group), Ad‑HIF‑1α (Ad‑HIF‑1α group) or Ad‑HIF‑1α in addition to erythropoietin mimetic peptide‑9 (EMP9), an EPO‑receptor (‑R) antagonist (Ad‑HIF‑1α+EMP9 group), were used for an intracranial injection into rat ischemic penumbra 1 h following MCAO. All rats demonstrated functional improvement following tMCAO, while the improvement rate was faster in rats treated by Ad‑HIF‑1α compared with all other groups. The EPO‑R inhibitor partially reversed the benefits of Ad‑HIF‑1α. Apoptosis induced by tMCAO was significantly inhibited by Ad‑HIF‑1α (P<0.05). The expression of HIF‑1α, evaluated by immunohistochemistry either in neurons or astrocytes, was upregulated by Ad‑HIF‑1α. Both EPO mRNA and protein expression were increased by Ad‑HIF‑1α, however, there was no significant change of EPO‑R either on an mRNA level or protein level. Furthermore, EMP9 did not change the EPO expression which was upregulated by Ad‑HIF‑1α. Activated caspase 3 in neurons was suppressed by Ad‑HIF‑1α. Activated caspase 3 downregulated by HIF‑1α was partially blocked by EMP9. Altogether, the present data demonstrated that HIF‑1α attenuates neuronal apoptosis partially through upregulating EPO following cerebral ischemia in rat. Thus, upregulating HIF‑1α subsequent to a stroke may be a potential treatment for ischemic stroke.
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