ArticleStroke2018
Focal Cerebral Ischemia and Reperfusion Induce Brain Injury Through α2δ-1-Bound NMDA Receptors.
Article in Stroke, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- HIV-1 gp120 Induces Nociceptive Hypersensitivity via α2δ-1-Bound NMDA Receptors at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Efficacy of pregabalin in the treatment of acute cerebral hemorrhage and its influence on prognosis.Frontiers in pharmacology · 2026Article
- RCAN1-Mediated Calcineurin Impairment Drives Sympathetic Outflow in Hypertension.Circulation research · 2025Article
- Unraveling the Role of α2δ-1 in Cerebral Hemorrhage: Calcium Overload, Endoplasmic Reticulum Stress, and Microglial Apoptosis.Brain and behavior · 2025Article
- α2δ-2 regulates synaptic GluK1 kainate receptors in Purkinje cells and motor coordination.Brain : a journal of neurology · 2025Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Kynurenic acid protects against ischemia/reperfusion injury by modulating apoptosis in cardiomyocytes.Apoptosis : an international journal on programmed cell death · 2024Article
- Calcineurin and CK2 Reciprocally Regulate Synaptic AMPA Receptor Phenotypes via α2δ-1 in Spinal Excitatory Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Calcineurin regulates synaptic CaThe Journal of physiology · 2024Article
- Quercetin alleviates chronic unpredictable mild stress-induced depression-like behavior by inhibiting NMDAR1 with α2δ-1 in rats.CNS neuroscience & therapeutics · 2024Article
- Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- SIRT1-regulated ROS generation activates NMDAR2B phosphorylation to promote central sensitization and allodynia in a male chronic migraine rat model.Frontiers in molecular neuroscience · 2024Article
- GluN2B-containing NMDA receptor attenuated neuronal apoptosis in the mouse model of HIBD through inhibiting endoplasmic reticulum stress-activated PERK/eIF2α signaling pathway.Frontiers in molecular neuroscience · 2024Article
- The NR2B-targeted intervention alleviates the neuronal injuries at the sub-acute stage of cerebral ischemia: an exploration of stage-dependent strategy against ischemic insults.Experimental brain research · 2023Article
- Article
- Brain α2δ-1-Bound NMDA Receptors Drive Calcineurin Inhibitor-Induced Hypertension.Circulation research · 2023Article
- Neuroinflammatory Biomarkers in the Brain, Cerebrospinal Fluid, and Blood After Ischemic Stroke.Molecular neurobiology · 2023Review
- Expression profiles of α-synuclein in cortical lesions of patients with FCD IIb and TSC, and FCD rats.Frontiers in neurology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Background and Purpose- Glutamate NMDARs (N-methyl-D-aspartate receptors) play a major role in the initiation of ischemic brain damage. However, NMDAR antagonists have no protective effects in stroke patients, possibly because they impair physiological functions of NMDARs. α2δ-1 (encoded by Cacna2d1) is strongly expressed in many brain regions. We determined the contribution of α2δ-1 to NMDAR hyperactivity and brain injury induced by ischemia and reperfusion. Methods- Mice were subjected to 90 minutes of middle cerebral artery occlusion followed by 24 hours of reperfusion. Neurological deficits, brain infarct volumes, and calpain/caspase-3 activity in brain tissues were measured. NMDAR activity of hippocampal CA1 neurons was measured in an in vitro ischemic model. Results- Middle cerebral artery occlusion increased α2δ-1 protein glycosylation in the cerebral cortex, hippocampus, and striatum. Coimmunoprecipitation showed that ischemia rapidly enhanced the α2δ-1-NMDAR physical interaction in the mouse brain tissue. Inhibiting α2δ-1 with gabapentin, uncoupling the α2δ-1-NMDAR interaction with an α2δ-1 C terminus-interfering peptide, or genetically ablating Cacna2d1 had no effect on basal NMDAR currents but strikingly abolished oxygen-glucose deprivation-induced NMDAR hyperactivity in hippocampal CA1 neurons. Systemic treatment with gabapentin or α2δ-1 C-terminus-interfering peptide or Cacna2d1 genetic knock-out reduced middle cerebral artery occlusion-induced infarct volumes, neurological deficit scores, and calpain/caspase-3 activation in brain tissues. Conclusions- α2δ-1 is essential for brain ischemia-induced neuronal NMDAR hyperactivity, and α2δ-1-bound NMDARs mediate brain damage caused by cerebral ischemia. Targeting α2δ-1-bound NMDARs, without impairing physiological α2δ-1-free NMDARs, may be a promising strategy for treating 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 OpenQuestion graph.