Hydrogen-rich saline mediates neuroprotection through the regulation of endoplasmic reticulum stress and autophagy under hypoxia-ischemia neonatal brain injury in mice

Bai, Xuemei; Song, Lingyun; Yuan, Lin; Xie, Yunkai; Li, Tong; Wang, Lingxiao; Wang, Xueer; Zhang, Tiantian; Qin, Shucun; Song, Guohau; Ge, Li; Wang, Zhen

doi:10.1016/j.brainres.2016.06.020

Cited by 61 publications

(56 citation statements)

References 37 publications

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“…The model used in this study was based on the Rice–Vannucci model [18], with minor modifications as described in our previous publication [19]. Briefly, C57 mouse pups (postnatal day 7) were anesthetized under 2.5% isoflurane; then, the right common carotid artery was exposed, and ligation was performed.…”

Section: Methodsmentioning

confidence: 99%

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Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress

et al. 2017

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Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H2S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H2S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H2S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72 h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER) stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H2S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI.

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Section: Methodsmentioning

confidence: 99%

“…In the first experiment, each brain was sliced coronally and processed with 2% TTC staining, and infract volume quantification was carried out as previously described [19].…”

Section: Methodsmentioning

confidence: 99%

Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress

et al. 2017

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“…Last but not least, as H2 is an endogenous substance, the goal of better tissue compatibility than other anti-viral drugs can be achieved [54][55][56].…”

Section: Novel Vaca S1d Signal Sequence Found In Helicobacter Pylori mentioning

confidence: 99%

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

Hu¹

2017

SOJMID

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Hydrogen, a non-cytotoxic molecule, is one of nature's most simple elements [1,2]. Recent studies revealed that intraperitoneal injection of hydrogen-rich saline has surprising anti-inflammation, anti-oxidant, anti-apoptosis effects and protected organism against polymicrobial sepsis injury, acute peritonitis injury both by reducing oxidative stress and via decreasing mass proinflammatory responses. It is also well known that the majority of viral -induced tissue damage and discomfort are mainly caused by an inflammatory cytokine storm and oxidative stress rather than by virus itself [3][4][5]. Studies have shown that suppressing the cytokine storm and reducing oxidative stress can significantly alleviate the symptoms of influenza and other severe viral infections diseases [3][4][5][6][7]. However, none of the studies have been focused on the solution as an anti-virus infection therapy yet. Therefore, we hypothesize that hydrogen-rich solution therapy may be a safe, reliable, and effective treatment for Multiple Organ Dysfunction Syndrome (MODS) induced by influenza and other viral infectious diseases.

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“…In our previous study, we found that HS administration could reduce retinal excitotoxic injury and promote retinal recovery in glutamate-induced excitotoxic injury guinea pig model [21]. We also found that HS exerts neuroprotection against hypoxic-ischemic brain damage in neonatal mouse [22]. In addition, HS has potential therapeutic effects on contusive SCI [23, 24] and spinal cord ischemia-reperfusion injury [25].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats

Wei

Cheng

et al. 2017

Oncotarget

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To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11–T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells.

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Hydrogen-rich saline mediates neuroprotection through the regulation of endoplasmic reticulum stress and autophagy under hypoxia-ischemia neonatal brain injury in mice

Cited by 61 publications

References 37 publications

Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress

Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats

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