Video Experimental Relacionado

Updated: Jan 8, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Published on: November 6, 2017

LRRC8A media la lesión neuronal isquémica al potenciar la actividad del receptor NMDA y activar la vía apoptótica

Chengli Qian^1,2, Linshu Huang¹, Ying Chen¹

¹Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Cell biology international

|December 22, 2025

Abstract:

Brain ischemia induces neuronal apoptosis, a key event in stroke pathology, but the underlying mechanisms remain incompletely understood. This study investigates the role of the volume-regulated anion channel subunit leucine-rich repeat-containing protein 8 A (LRRC8A) in ischemia-induced neuronal damage. In a rat model of middle cerebral artery occlusion (MCAO) and in cultured neurons under oxygen-glucose deprivation (OGD), ischemia/hypoxia rapidly upregulated LRRC8A expression in apoptotic neurons. Knockdown of lrrc8a via small interfering RNA (siRNA) attenuated brain infarction, improved neurological deficits, and reduced neuronal apoptosis. Mechanistically, lrrc8a knockdown suppressed the activation of the mitochondrial Bax/Bcl-2/Caspase-9/Caspase-3 apoptotic pathway. Furthermore, lrrc8a knockdown reversed OGD-induced hyperactivation of NMDA receptors (NMDARs) and weakened the enhanced interaction between LRRC8A and the obligatory NMDAR subunit GluN1, which was predicted by structural modeling. These findings reveal that cerebral ischemia upregulates neuronal LRRC8A, which may promote NMDAR hyperactivity via interaction with GluN1, thereby triggering mitochondrial apoptosis. LRRC8A represents a potential therapeutic target for mitigating neuronal apoptosis in ischemic stroke.

Palabras clave:

LRRC8A receptores NMDA VRACs isquemia cerebral apoptosis neuronal

Más Videos Relacionados

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

Videos de Conceptos Relacionados

The Extrinsic Apoptotic Pathway

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

Necrosis

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...