ArticleThe Journal of pharmacology and experimental therapeutics2011
Characterization of neuroprotective effects of biphalin, an opioid receptor agonist, in a model of focal brain ischemia.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
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
25 citing papers in PubMed, 44 citations in OpenAlex.
- Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.Pharmaceutics · 2022Review
- Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.International journal of molecular sciences · 2022Review
- Biphalin-A Potent Opioid Agonist-As a Panacea for Opioid System-Dependent Pathophysiological Diseases?International journal of molecular sciences · 2021Review
- Targeting Common Signaling Pathways for the Treatment of Stroke and Alzheimer's: a Comprehensive Review.Neurotoxicity research · 2021Review
- Carnosine Protects against Cerebral Ischemic Injury by Inhibiting Matrix-Metalloproteinases.International journal of molecular sciences · 2021Article
- Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke.Pharmaceutics · 2020Review
- Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists.Biomolecules · 2020Article
- Kappa opioid receptor agonists improve postoperative cognitive dysfunction in rats via the JAK2/STAT3 signaling pathway.International journal of molecular medicine · 2019Article
- Brain Delivery of a Potent Opioid Receptor Agonist, Biphalin during Ischemic Stroke: Role of Organic Anion Transporting Polypeptide (OATP).Pharmaceutics · 2019Article
- Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity.Pharmaceutics · 2018Review
- Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?Redox biology · 2017Article
- Biphalin, a Dimeric Enkephalin, Alleviates LPS-Induced Activation in Rat Primary Microglial Cultures in Opioid Receptor-Dependent and Receptor-Independent Manners.Neural plasticity · 2017Article
- Effects of the Hybridization of Opioid and Neurotensin Pharmacophores on Cell Survival in Rat Organotypic Hippocampal Slice Cultures.Neurotoxicity research · 2015Article
- Peptides at the blood brain barrier: Knowing me knowing you.Peptides · 2015Review
- Critical role of sphingosine-1-phosphate receptor-2 in the disruption of cerebrovascular integrity in experimental stroke.Nature communications · 2015Article
- In vitro and in vivo efficacy of a potent opioid receptor agonist, biphalin, compared to subtype-selective opioid receptor agonists for stroke treatment.Brain research · 2015Article
- Nicotine pre-exposure reduces stroke-induced glucose transporter-1 activity at the blood-brain barrier in mice.Fluids and barriers of the CNS · 2015Article
- Common mechanisms of Alzheimer's disease and ischemic stroke: the role of protein kinase C in the progression of age-related neurodegeneration.Journal of Alzheimer's disease : JAD · 2015Review
- Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases.Current neuropharmacology · 2015Review
- Drug delivery to the ischemic brain.Advances in pharmacology (San Diego, Calif.) · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Approximately 795,000 people experience a new or recurrent stroke in the United States annually. The purpose of this study was to assess the protective effect of a nonselective opioid receptor agonist, biphalin, in brain edema and infarct damage by using both in vitro and in vivo models of stroke. In an in vivo model of ischemia, biphalin significantly decreased edema (66.6 and 58.3%) and infarct (52.2 and 56.4%) ratios in mouse transient (60-min occlusion/24-h reperfusion) and permanent (6 h) middle cerebral artery occlusion models, respectively. Biphalin administration also showed decreased neurodegeneration in hippocampal, cortical, and striatal brain tissue after ischemia, evidenced by reduced Fluoro-Jade C staining. In addition, biphalin improved neurological function after stroke injury evidenced by neurological score and locomotor activity evaluation. Biphalin significantly decreased penumbral expression of Na(+), K(+), 2Cl(-) cotransporter (NKCC) and the translocation of the conventional isoforms of protein kinase C (PKC). It also reversed the activation of PKC-induced cell volume increase during ischemia in primary neuronal cell cultures exposed to 1 h of oxygen glucose deprivation. These data suggest that opioid receptor activation provides neuroprotection during stroke, and a possible explanation of this mechanism could be the inhibition of NKCC function via the regulation of PKC-dependent cell signaling.
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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.