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Cited by 16

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

Ovcjak, Andrea, Xiao, Aijiao, Kim, Ji-Sun, Xu, Baofeng, Szeto, Vivian, Turlova, Ekaterina, Abussaud, Ahmed, Chen, Nai-hong, Miller, Steven P., Sun, Hong-Shuo, Feng, Zhong-Ping·2022·Experimental Neurology
DOI 10.1016/j.expneurol.2022.113985
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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.

Overview

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Crossref · 10.1016/j.expneurol.2022.113985

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103 of 103 references verified0 citation errors · 0 not checkable

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Citations

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1 retracted

Research works printed but not linked: 4

  1. Gursoy, 2020, Investigation of the possible protective effects of ketamine and Dantrolene on the hippocampal apoptosis and spatial learning in rats exposed to repeated electroconvulsive seizures as a model of status epilepticus, Turk. Neurosurg., 30, 871
  2. Hua Wang, 2002, Roles of protein kinase C and inositol(1,4,5)-trisphosphate in the pathogenesis of hypoxic- ischemic brain injury in neonatal rats - PubMed, Chin. Med. J., 116, 829
  3. Johnston, 1995, Hypoxic and ischemic central nervous system disorders in infants and Childrenin infants and children - PubMed, Adv. Pediatr. Infect. Dis., 42, 1
  4. Mennerich, 2014, Direct phosphorylation events involved in HIF-alpha regulation: the role of GSK-3beta, Hypoxia, 2, 45

Cited by

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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
DOI
10.1016/j.expneurol.2022.113985
Cited by
16
References
103
Language
en
Licence

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