ArticleStem cells (Dayton, Ohio)2015
PACAP38/PAC1 signaling induces bone marrow-derived cells homing to ischemic brain.
Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- The neuropeptide in ischemic brain injury: insights, challenges, and horizon of targeted interventions.Journal of translational medicine · 2026Pooled it
- Moderate Exercise Stimulates PACAP-Mediated Neurogenesis in Rat Dentate Gyrus and Cerebellar Cortex.Journal of functional morphology and kinesiology · 2026Article
- HIF‑1α in cerebral ischemia (Review).Molecular medicine reports · 2022Review
- PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.Frontiers in immunology · 2021Article
- Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke.Aging and disease · 2020Review
- Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood-Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Show Me Your Friends and I Tell You Who You Are: The Many Facets of Prion Protein in Stroke.Cells · 2020Review
- Intranasal Administration of PACAP Is an Efficient Delivery Route to Reduce Infarct Volume and Promote Functional Recovery After Transient and Permanent Middle Cerebral Artery Occlusion.Frontiers in endocrinology · 2020Article
- Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service.Journal of clinical medicine · 2019Review
- Alteration of the PAC1 Receptor Expression in the Basal Ganglia of MPTP-Induced Parkinsonian Macaque Monkeys.Neurotoxicity research · 2018Article
- Protective effects of PACAP in ischemia.The journal of headache and pain · 2018Review
- PACAP Modulates Expression of Hypoxia-Inducible Factors in Streptozotocin-Induced Diabetic Rat Retina.Journal of molecular neuroscience : MN · 2015Article
- Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding stem cell homing, which is governed by environmental signals from the surrounding niche, is important for developing effective stem cell-based repair strategies. The molecular mechanism by which the brain under ischemic stress recruits bone marrow-derived cells (BMDCs) to the vascular niche remains poorly characterized. Here we report that hypoxia-inducible factor-1α (HIF-1α) activation upregulates pituitary adenylate cyclase-activating peptide 38 (PACAP38), which in turn activates PACAP type 1 receptor (PAC1) under hypoxia in vitro and cerebral ischemia in vivo. BMDCs homing to endothelial cells in the ischemic brain are mediated by HIF-1α activation of the PACAP38-PAC1 signaling cascade followed by upregulation of cellular prion protein and α6-integrin to enhance the ability of BMDCs to bind laminin in the vascular niche. Exogenous PACAP38 confers a similar effect in facilitating BMDCs homing into the ischemic brain, resulting in reduction of ischemic brain injury. These findings suggest a novel HIF-1α-activated PACAP38-PAC1 signaling process in initiating BMDCs homing into the ischemic brain for reducing brain injury and enhancing functional recovery after ischemic stroke.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.