ArticleAging2019
Dexmedetomidine inhibits neuronal apoptosis by inducing Sigma-1 receptor signaling in cerebral ischemia-reperfusion injury.
Article in Aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Effect of dexmedetomidine on postoperative cognitive function in patients with gastrointestinal cancer: a meta-analysis of randomized controlled trials.Frontiers in neurologyPooled it
- A randomized controlled trial investigating the impact of early goal-directed sedation dominated by dexmedetomidine on cerebral oxygen metabolism and inflammatory mediators in patients with severe brain injury.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Trial
- Dexmedetomidine Exerts Multi-level Effects to Ameliorate Alzheimer's Disease Pathology in the Adult Zebrafish Brain.Molecular neurobiology · 2026Article
- Potential neuroprotective role of dexmedetomidine in preventing postoperative cerebral hyperperfusion syndrome: from mechanisms to clinical applications.American journal of translational research · 2026Review
- Neuroprotective mechanisms of dexmedetomidine in perioperative neurocognitive disorders: From molecular pathways to clinical translation.Journal of anesthesia and translational medicine · 2025Review
- Investigation of the mechanism by which sigma-1 receptor protein mediates the IRE1-XBP-1s pathway to alleviate cerebral ischemia-reperfusion injury.European journal of medical research · 2025Article
- Targeting the sigma-1 receptor with pridopidine induces functional neurorestoration in spinal cord ischemia-reperfusion injury.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Dexmedetomidine Improves Long-term Neurological Outcomes by Promoting Oligodendrocyte Genesis and Myelination in Neonatal Rats Following Hypoxic-ischemic Brain Injury.Molecular neurobiology · 2025Article
- Dexmedetomidine and the glymphatic system: a new perspective in managing postoperative cognitive dysfunction.Frontiers in pharmacology · 2025Review
- Anesthetics in pathological cerebrovascular conditions.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Review
- The Role of Intravenous Anesthetics for Neuro: Protection or Toxicity?Neuroscience bulletin · 2025Review
- Protective Effects of Trimetazidine and Dexmedetomidine on Liver Injury in a Mesenteric Artery Ischemia-Reperfusion Rat Model via Endoplasmic Reticulum Stress.Biomedicines · 2024Article
- TREK-1 channel as a therapeutic target for dexmedetomidine-mediated neuroprotection in cerebral ischemia.Neurogenetics · 2024Article
- The role of anesthesia in peri‑operative neurocognitive disorders: Molecular mechanisms and preventive strategies.Fundamental research · 2024Review
- Endoplasmic reticulum stress and the unfolded protein response: emerging regulators in progression of traumatic brain injury.Cell death & disease · 2024Review
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- Effect of dexmedetomidine on ncRNA and mRNA profiles of cerebral ischemia-reperfusion injury in transient middle cerebral artery occlusion rats model.Frontiers in pharmacology · 2024Article
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dexmedetomidine is known to alleviate cerebral ischemia-reperfusion injury (CIRI). We established a rat model of CIRI, which exhibited higher neurological deficit scores and a greater number of apoptotic cells in the cerebral ischemic penumbra than controls. Dexmedetomidine reversed the neuronal apoptosis and improved neurological function in this model. We then examined Sigma-1 receptor (Sig-1R) expression on the endoplasmic reticulum (ER) in brain tissues at different reperfusion time points. Sig-1R expression increased with CIRI and decreased with increasing reperfusion times. After 24 hours of reperfusion, dexmedetomidine upregulated Sig-1R expression, and ER stress proteins (GRP78, CHOP, JNK and Caspase-3) were detected in brain tissues with Western blotting. Moreover, GRP78 expression followed a pattern similar to Sig-1R. Dexmedetomidine induced GRP78 expression but inhibited CHOP, Caspase-3 and phosphorylated-JNK expression in brain tissues. A Sig-1R-specific inhibitor reduced GRP78 expression and partially inhibited the upregulation of GRP78 by dexmedetomidine. The inhibitor also increased CHOP and Caspase-3 expression and partially reversed the inhibitory effects of dexmedetomidine on these pro-apoptotic ER stress proteins. These results suggest that dexmedetomidine at least partially inhibits ER stress-induced apoptosis by activating Sig-1R, thereby attenuating brain damage after 24 hours of ischemia-reperfusion.
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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 OpenQuestion graph.