The DOI matches its Crossref record; 103 of the 103 references it cites were found in a registry or an index.
Ryanodine receptor inhibitor dantrolene reduces hypoxic-ischemic brain injury in neonatal mice
Abstract
Ryanodine receptors (RyR) located on the membrane of the endoplasmic reticulum (ER), are a potent regulator of intracellular calcium levels upon activation. Dysregulated Ca 2+ homeostasis is characteristic of hypoxic-ischemic (HI) brain injury and ultimately leads to neurodegeneration. RyRs have thereby been implicated in the Ca 2+ imbalance that occurs during and after HI. In this study, we investigated the effects of RyR antagonist, dantrolene, on HI brain injury in neonatal mice. We found that administration of dantrolene (i.p.) on postnatal day 7 mice reduced the infarction volume and morphological damage induced by HI, and improved functional recovery as assessed by neurobehavioral testing. The neuroprotective effect of dantrolene was further demonstrated in neuronal cell culture in vitro, where dantrolene significantly reduced oxygen-glucose deprivation (OGD)-induced cell death. Fura-2 calcium imaging confirmed that dantrolene reduced the intracellular calcium level in cultured cortical neurons in vitro. Finally, Western blot analysis showed that dantrolene treatment reduced cleaved caspase-3 and -9 apoptotic proteins, and elevated pro-survival protein kinase C (PKC) protein levels. Taken together, our results demonstrate that dantrolene exerts neuroprotective effects against neonatal HI brain injury. This suggests that RyRs play a role in mediating the ionic imbalance induced by HI and therefore represent a potential target for drug development.
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“Short-term neurobehavioral tests were applied 24 h after HI injury by observers who were blind to the experiments [18].”
From Engineered Extracellular Vesicles Loaded with MiR-100-5p Antagonist Selectively Target the Lesioned Region to Promote Recovery from Brain Damage (2025) · cites this paper as [18]
Citations
Cites
1 retracted
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Research works printed but not linked: 4
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Cited by
Cheng, Y., Gai, C., Zhao, Y., Li, T., Song, Y., Luo, Q., Xin, D., Jiang, Z., Chen, W., Liu, D., et al. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01376-6 · Cited by 5
Metadata
- Authors
- Ovcjak, A., Xiao, A., Kim, J.-S., Xu, B., Szeto, V., Turlova, E., Abussaud, A., Chen, N.-H., Miller, S. P., Sun, H.-S., & Feng, Z.-P.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 351
- Pages
- 113985
- ISSN
- 0014-4886
- Cited by
- 16
- References
- 103
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
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- Ovcjak, A., Xiao, A., Kim, J.-S., Xu, B., Szeto, V., Turlova, E., Abussaud, A., Chen, N.-H., Miller, S. P., Sun, H.-S., & Feng, Z.-P. (2022). Ryanodine receptor inhibitor dantrolene reduces hypoxic-ischemic brain injury in neonatal mice. Experimental Neurology. https://doi.org/10.1016/j.expneurol.2022.113985
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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