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Updated: Sep 14, 2026
Mouse Cardiac Arrest Model for Brain Imaging and Brain Physiology Monitoring During Ischemia and Resuscitation
Published on: April 14, 2023
ELAVL3 Exacerbates Brain Injury and Cognitive Dysfunction in Mice After Cardiac Arrest by Increasing S100B mRNA
Background And Aims:
Microglial activation-driven neuroinflammation exacerbates secondary brain injury following cerebral ischemia/reperfusion (I/R). The underlying molecular regulators are not fully elucidated. We investigated the role of the RNA-binding protein ELAVL3 and its target S100B in post-ischemic microglial activation and subsequent neuronal injury.
Methods:
In vitro, BV-2 microglia were subjected to oxygen-glucose deprivation/reperfusion (OGD/R), and their conditioned medium was applied to HT22 neurons. In vivo, a mouse model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) was utilized. Gene expression was modulated using small interfering RNA (siRNA), plasmids, and lentiviral vectors. The ELAVL3-S100B mRNA interaction was confirmed by RNA immunoprecipitation and luciferase assays. Neuronal injury, neuroinflammation, and cognitive outcomes were evaluated using molecular, histological, and behavioral analyses.
Results:
OGD/R induced pro-inflammatory activation in microglia, leading to neuronal apoptosis, oxidative stress, and mitochondrial damage. ELAVL3 and S100B were upregulated in activated microglia in vitro and in the hippocampus after CA/CPR. ELAVL3 directly bound the S100B 3'-untranslated region, enhancing its mRNA stability and protein expression. In vitro, ELAVL3 knockdown suppressed S100B, attenuated microglial activation, and protected neurons. In vivo, hippocampal knockdown of either ELAVL3 or S100B reduced neuroinflammation and improved cognitive function after CA/CPR. The neuroprotective effects of ELAVL3 knockdown were rescued by S100B overexpression.
Conclusion:
Our study identifies the ELAVL3/S100B axis as a key driver of post-ischemic neuroinflammation. ELAVL3 enhances S100B expression post-transcriptionally, promoting microglial-mediated neurotoxicity. Targeting this pathway may offer a potential therapeutic strategy for cerebral ischemic injuries.
