Edaravone Alleviated Propofol-Induced Neurotoxicity in Developing Hippocampus by MBDNF/TrkB/PI3K Pathway

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2021 Apr 9

PMID 33833500

Citations 5

Authors

Yangliang Yang

Jing Yi

Mengzhi Pan

Baoji Hu

Hongwei Duan

Affiliations

Soon will be listed here.

Abstract

Background: To investigate the neuroprotective effect of edaravone on excessive-dose propofol-induced neurotoxicity in the hippocampus of newborn rats and HT22 cells.

Methods: Cell proliferation was investigated by assessing ki67 expression in the neural stem of the hippocampus of newborn rats and by cell counting kit-8 (CCK8) assay in HT22 cells. Cell apoptosis was assessed in vivo by caspase 3 detection in Western blots and measurement of apoptosis in neurons and glial cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Apoptosis was analyzed by flow cytometry in HT22 cells. The Morris water maze was used to evaluate the long-term learning and memory ability of rats. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expression of mBDNF/TrkB/PI3K pathway-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction (q-RT PCR).

Results: In neonatal rat hippocampus and HT22 cells, edaravone increased cell proliferation and decreased cell apoptosis after excessive propofol-induced neurotoxicity. In addition, the levels of proinflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF)-α were reduced by edaravone pretreatment. The use of the tropomyosin receptor kinase B (TrkB) antagonist ANA-12 and TrkB agonist 7,8DHF with propofol groups showed that edaravone mitigated excessive propofol-induced neurotoxicity through the mature brain-derived neurotrophic factor (mBDNF)/TrkB/phosphoinositide 3-kinase (PI3K) pathway. However, the current dose of propofol did not significantly affect long-term learning and memory in rats.

Conclusion: Edaravone pretreatment ameliorated propofol-induced proliferation inhibition, neuroapoptosis, and neural inflammation by activating the mBDNF/TrkB/PI3K pathway.

Citing Articles

Edaravone Confers Neuroprotective, Anti-inflammatory, and Antioxidant Effects on the Fetal Brain of a Placental-ischemia Mouse Model.

Atallah M, Yamashita T, Hu X, Hu X, Abe K J Neuroimmune Pharmacol. 2023; 18(4):640-656.

PMID: 37924374 DOI: 10.1007/s11481-023-10095-6.

Effects of Subchronic Propofol Administration on the Proliferation and Differentiation of Neural Stem Cells in Rat Hippocampus.

Chang C, Bai W, Li J, Huo S, Wang T, Shao J Curr Ther Res Clin Exp. 2023; 98:100691.

PMID: 36798524 PMC: 9925857. DOI: 10.1016/j.curtheres.2023.100691.

Esketamine improves propofol-induced brain injury and cognitive impairment in rats.

Xu G, Wang Y, Chen Z, Zhang Y, Zhang X, Zhang G Transl Neurosci. 2022; 13(1):430-439.

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The propofol-induced mitochondrial damage in fetal rat hippocampal neurons via the AMPK/P53 signaling pathway.

Xiao F, Qin Y, Chen J, Li C, Qin Y, Wei Y Ann Transl Med. 2022; 10(20):1106.

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An Integrative Bioinformatics Analysis of the Potential Mechanisms Involved in Propofol Affecting Hippocampal Neuronal Cells.

Zhuang Z, Li D, Jiang M, Wang Y, Cao Q, Li S Comput Intell Neurosci. 2022; 2022:4911773.

PMID: 35515499 PMC: 9064519. DOI: 10.1155/2022/4911773.

References

Bai X, Zhang C, Chen A, Liu W, Li J, Sun Q . Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons. Neural Plast. 2016; 2016:4034218. PMC: 5121579. DOI: 10.1155/2016/4034218. View

Li J, Guo M, Liu Y, Wu G, Miao L, Zhang J . Both GSK-3β/CRMP2 and CDK5/CRMP2 Pathways Participate in the Protection of Dexmedetomidine Against Propofol-Induced Learning and Memory Impairment in Neonatal Rats. Toxicol Sci. 2019; 171(1):193-210. DOI: 10.1093/toxsci/kfz135. View

Kojima M, Otabi H, Kumanogoh H, Toyoda A, Ikawa M, Okabe M . Reduction in BDNF from Inefficient Precursor Conversion Influences Nest Building and Promotes Depressive-Like Behavior in Mice. Int J Mol Sci. 2020; 21(11). PMC: 7312902. DOI: 10.3390/ijms21113984. View

Xu F, Ma R, Zhang G, Wang S, Yin J, Wang E . Estrogen and propofol combination therapy inhibits endoplasmic reticulum stress and remarkably attenuates cerebral ischemia-reperfusion injury and OGD injury in hippocampus. Biomed Pharmacother. 2018; 108:1596-1606. DOI: 10.1016/j.biopha.2018.09.167. View

Ni G, Liang C, Wang J, Duan C, Wang P, Wang Y . Astragaloside IV improves neurobehavior and promotes hippocampal neurogenesis in MCAO rats though BDNF-TrkB signaling pathway. Biomed Pharmacother. 2020; 130:110353. DOI: 10.1016/j.biopha.2020.110353. View

Zhao X, Zhang E, Ren X, Bai X, Wang D, Bai L . Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway. Biol Res. 2020; 53(1):28. PMC: 7333427. DOI: 10.1186/s40659-020-00297-0. View

Ishiguro M, Kobayashi S, Matsuyama K, Nagamine T . Effects of propofol on IPSCs in CA1 and dentate gyrus cells of rat hippocampus: Propofol effects on hippocampal cells' IPSCs. Neurosci Res. 2018; 143:13-19. DOI: 10.1016/j.neures.2018.05.003. View

Wang G, Su J, Li L, Feng J, Shi L, He W . Edaravone alleviates hypoxia-acidosis/reoxygenation-induced neuronal injury by activating ERK1/2. Neurosci Lett. 2013; 543:72-7. DOI: 10.1016/j.neulet.2013.02.067. View

Zhou J, Wang F, Zhang J, Li J, Ma L, Dong T . The interplay of BDNF-TrkB with NMDA receptor in propofol-induced cognition dysfunction : Mechanism for the effects of propofol on cognitive function. BMC Anesthesiol. 2018; 18(1):35. PMC: 5887174. DOI: 10.1186/s12871-018-0491-y. View

10.

Jangra A, Kwatra M, Singh T, Pant R, Kushwah P, Ahmed S . Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus. Eur J Pharmacol. 2016; 791:51-61. DOI: 10.1016/j.ejphar.2016.08.003. View

11.

Shi X, Ohta Y, Shang J, Morihara R, Nakano Y, Fukui Y . Neuroprotective effects of SMTP-44D in mice stroke model in relation to neurovascular unit and trophic coupling. J Neurosci Res. 2018; 96(12):1887-1899. DOI: 10.1002/jnr.24326. View

12.

Hao L, Dong L, Yu Q, Shen W, Wei X . Edaravone inhibits procaspase-3 denitrosylation and activation through FasL-Trx2 pathway in KA-induced seizure. Fundam Clin Pharmacol. 2020; 34(6):662-670. DOI: 10.1111/fcp.12556. View

13.

Minnelli C, Laudadio E, Galeazzi R, Rusciano D, Armeni T, Stipa P . Synthesis, Characterization and Antioxidant Properties of a New Lipophilic Derivative of Edaravone. Antioxidants (Basel). 2019; 8(8). PMC: 6720979. DOI: 10.3390/antiox8080258. View

14.

Upton D, Popovic K, Fulton R, Kassiou M . Anaesthetic-dependent changes in gene expression following acute and chronic exposure in the rodent brain. Sci Rep. 2020; 10(1):9366. PMC: 7283325. DOI: 10.1038/s41598-020-66122-6. View

15.

Liu F, Liu S, Patterson T, Fogle C, Hanig J, Wang C . Protective Effects of Xenon on Propofol-Induced Neurotoxicity in Human Neural Stem Cell-Derived Models. Mol Neurobiol. 2019; 57(1):200-207. DOI: 10.1007/s12035-019-01769-5. View

16.

Wang T, Zhu H, Hou Y, Gu W, Wu H, Luan Y . Galantamine reversed early postoperative cognitive deficit via alleviating inflammation and enhancing synaptic transmission in mouse hippocampus. Eur J Pharmacol. 2018; 846:63-72. DOI: 10.1016/j.ejphar.2018.12.034. View

17.

Zhang C, Wang Y, Jin J, Li K . Erythropoietin protects propofol induced neuronal injury in developing rats by regulating TLR4/NF-κB signaling pathway abstract. Neurosci Lett. 2019; 712:134517. DOI: 10.1016/j.neulet.2019.134517. View

18.

Yang L, Ton H, Zhao R, Geron E, Li M, Dong Y . Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice. Sci Rep. 2020; 10(1):11226. PMC: 7343864. DOI: 10.1038/s41598-020-66959-x. View

19.

Guo Z, Wu H, Li X, Yu Y, Gu R, Lan R . Edaravone protects rat astrocytes from oxidative or neurotoxic inflammatory insults by restoring Akt/Bcl-2/Caspase-3 signaling axis. IBRO Rep. 2020; 8:122-128. PMC: 7200465. DOI: 10.1016/j.ibror.2020.04.003. View

20.

Wu C, Lu J, Lu S, Huang M, Xu Y . Increased ratio of mature BDNF to precursor-BDNF in patients with major depressive disorder with severe anhedonia. J Psychiatr Res. 2020; 126:92-97. DOI: 10.1016/j.jpsychires.2020.05.010. View