ArticleAnnals of clinical and translational neurology2014
Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection.
Article in Annals of clinical and translational neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders.Journal of genetics · 2019Pooled it
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- Pharmacological effects and target analysis of Guipi wan in the treatment of cerebral ischemia-reperfusion injury.Frontiers in pharmacology · 2024Article
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- Pathological changes of brain oscillations following ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- Molecular mechanisms for the prevention and promoting the recovery from ischemic stroke by nutraceutical laminarin: A comparative transcriptomic approach.Frontiers in nutrition · 2022Article
- Experimental cortical stroke induces aberrant increase of sharp-wave-associated ripples in the hippocampus and disrupts cortico-hippocampal communication.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
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- Combined network pharmacology and virtual reverse pharmacology approaches for identification of potential targets to treat vascular dementia.Scientific reports · 2020Article
- The Nervous System Relevance of the Calcium Sensing Receptor in Health and Disease.Molecules (Basel, Switzerland) · 2019Review
- Exploring the Potential of Spherical Harmonics and PCVM for Compounds Activity Prediction.International journal of molecular sciences · 2019Article
- CTL-Derived Granzyme B Participates in Hippocampal Neuronal Apoptosis Induced by Cardiac Arrest and Resuscitation in Rats.Frontiers in neurology · 2019Article
- Calcilytic NPS 2143 Reduces Amyloid Secretion and Increases sAβPPα Release from PSEN1 Mutant iPSC-Derived Neurons.Journal of Alzheimer's disease : JAD · 2019Article
- Family C G-Protein-Coupled Receptors in Alzheimer's Disease and Therapeutic Implications.Frontiers in pharmacology · 2019Review
- The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.Nature reviews. Endocrinology · 2018Review
- WDL-RF: predicting bioactivities of ligand molecules acting with G protein-coupled receptors by combining weighted deep learning and random forest.Bioinformatics (Oxford, England) · 2018Article
- Black Rice (Experimental neurobiology · 2018Article
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Authors and funding
7 authors.
Funding
Abstract
objectIschemic brain injury is the leading cause for death and long-term disability in patients who suffer cardiac arrest and embolic stroke. Excitotoxicity and subsequent Ca(2+)-overload lead to ischemic neuron death. We explore a novel mechanism concerning the role of the excitatory extracellular calcium-sensing receptor (CaSR) in the induction of ischemic brain injury.
methodMice were exposed to forebrain ischemia and the actions of CaSR were determined after its genes were ablated specifically in hippocampal neurons or its activities were inhibited pharmacologically. Since the CaSR forms a heteromeric complex with the inhibitory type B γ-aminobutyric acid receptor 1 (GABABR1), we compared neuronal responses to ischemia in mice deficient in CaSR, GABABR1, or both, and in mice injected locally or systemically with a specific CaSR antagonist (or calcilytic) in the presence or absence of a GABABR1 agonist (baclofen).
resultsBoth global and focal brain ischemia led to CaSR overexpression and GABABR1 downregulation in injured neurons. Genetic ablation of Casr genes or blocking CaSR activities by calcilytics rendered robust neuroprotection and preserved learning and memory functions in ischemic mice, partly by restoring GABABR1 expression. Concurrent ablation of Gabbr1 gene blocked the neuroprotection caused by the Casr gene knockout. Coinjection of calcilytics with baclofen synergistically enhanced neuroprotection. This combined therapy remained robust when given 6 h after ischemia.
interpretationOur study demonstrates a novel receptor interaction, which contributes to ischemic neuron death through CaSR upregulation and GABABR1 downregulation, and feasibility of neuroprotection by concurrently targeting these two receptors.
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