Dexamethasone Protects Against Ischaemic Brain Injury via Inhibiting the pAkt Signalling Pathway Through Increasing Hap1
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ORIGINAL ARTICLE
Dexamethasone Protects Against Ischaemic Brain Injury via Inhibiting the pAkt Signalling Pathway Through Increasing Hap1 Ning Xin 1 & Jun Lu 1 & Yanlong Zhou 1 & Yanbo Cheng 1 Received: 31 March 2020 / Revised: 15 June 2020 / Accepted: 25 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Dexamethasone has been reported to reduce the infarct volume and protect neurological function after ischaemic injury, but the mechanism of Dex in brain injury is not clear. We aimed to study the mechanism by which dexamethasone protects against ischaemic brain injury. Western blotting was to detected the expression of Hap1,TrkB, Akt and Erk; TTC staining to analyse ischemic volume; neurological deficit evaluation to test degree of ischemic injury; immunofluorescence staining to analyse the distribution of Hap1; and the MCAO model was used to study these processes. All data are expressed as the means ± SEM and were analysed by GraphPad Prism 6. P < 0.05 was considered statistically significant. After dexamethasone (Dex) treatment, Hap1 levels were increased and peaked at 2 days; then, we found that body weight was decreased in Hap1−/+ mice. Further study showed that Dex treatment reduced the ischaemic volume and improved neurological function. Finally, we showed that Hap1 regulated the levels of pTrkB, pAkt and pErk 1/2 in ischaemic injury after Dex treatment. Our data suggest that dexamethasone protects against ischaemic brain injury by inhibiting the pAkt signalling pathway through increasing Hap1. Keywords Dexamethasone . Hap1 . Stroke . Akt
Introduction Dexamethasone (Dex) is a common drug in the clinic, and it is an adrenal cortex hormone. It has anti-inflammatory (Dey and Bishayi 2019), anti-immune (May et al. 1990), anti-shock (Akiyama et al. 1984) and stress-relieving effects (Kumari et al. 2019), and it is widely used for the treatment of various clinical diseases. Dex has been reported to treat bacterial meningitis (Jaspan et al. 2010), relapsed and refractory multiple myeloma (RRMM) (Lee et al. 2020), rheumatoid arthritis (RA) (Ni et al. 2019), stroke and so on. In stroke, Dex can reduce the infarct volume and protect neurological function (Bertorelli et al. 1998; de Courten-Myers et al. 1994; Hyun et al. 2011); the mechanism maybe is that Dex treatment inhibits the expression of TNF-α and IL-1β, and involve in the NF-κB p65 pathway (Sun et al. 2018); however, this protection is only true for early administration, and there is no protective by later administration after ischemic injury (Norris
* Yanbo Cheng [email protected] 1
Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou City 221000, Jiangsu Province, China
and Hachinski 1986). Based on the discussions above, we propose that the early administration of dexamethasone is necessary for its protective role in models of ischaemia/ reperfusion (I/R) injury. Huntingtin-associated protein 1 (Hap1) was first identified by (Li et al. 1995), and it has been studied extensively
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