Hydrogen therapy reduces apoptosis in neonatal hypoxia–ischemia rat model

Jian-Hua, Cai; Kang, Zhiwei; Liu, Wenwu; Luo, Xu; Sun, Qiang; Zhang, Junyi; Ohta, Shigeo; Sun, Xuejun; Xu, Wei; Tao, Hengyi; Li, Runping

doi:10.1016/j.neulet.2008.05.077

Cited by 212 publications

(170 citation statements)

References 16 publications

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“…In the present study, we also found that the local administration of ouabain resulted in significant levels of cochlear SGN apoptosis as evidenced by TUNEL staining and caspase-3 activity, which could be significantly attenuated by H 2 treatment. Several previous studies have reported that H 2 has an anti-apoptotic role in many diseases [4,5,9] . Therefore, the results suggest that the protective roles of H 2 treatment may be associated with reduced SGN apoptosis.…”

Section: Discussionmentioning

confidence: 98%

“…Recently, many studies, including ours, have found that H 2 has therapeutic roles in many diseases via its ability to reduce oxidative stress, inflammation and apoptosis; these diseases include cerebral damage, spinal cord injury, sepsis, multiple organ dysfunction, chronic allograft nephropathy, tumors and type 2 diabetes [4][5][6][7][8][9][10][11][12][13][14] . Furthermore, H 2 can effectively protect against the morphological and functional cochlear hair cell damage induced by ROS [15] .…”

Section: Introductionmentioning

confidence: 97%

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Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

Xie

et al. 2012

Acta Pharmacol Sin

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Aim: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H 2 ), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. Methods: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H 2 treatment was given twice by exposing the animals to H 2 (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. Results: Treatment with H 2 (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H 2 treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H 2 (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H 2 treatment. However, ouabain did not change the morphology of cochlear hair cells. Conclusion:The results demonstrate that H 2 treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H 2 might be a potential agent for treating hearing impairment in AN patients.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

Xie

et al. 2012

Acta Pharmacol Sin

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“…There are several recent studies reported that molecular hydrogen reduced oxidative stress and its associated disorders. Molecular hydrogen in the form of gas or H 2 -saturated saline reduced the cerebral infarction (Ohsawa et al,2007) and decreased apoptosis in neonatal hypoxic brain injury in rats (Cai et al,2008;Cai et al,2009). Molecular hydrogen dissolved in drinking water similarly attenuated sclerotic lesions (Ohsawa et al,2008) and prevented cisplatin-induced nephrotoxicity in mice (Nakashima et al,2009).…”

Section: Introductionmentioning

confidence: 94%

Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress

et al. 2010

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Cao, Xue-jun Sun, Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress, Brain Research (2010Research ( ), doi: 10.1016Research ( /j.brainres.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2 AbstractThis study is to examine if hydrogen-rich saline reduced amyloid β (Aβ) induced neural inflammation, and learning and memory deficits in a rat model. S-D male rats (n = 84, 280-330g) were divided into three groups, sham operated, Aβ1-42 injected and Aβ1-42 plus hydrogen-rich saline treated animals. Hydrogen-rich saline (5 ml/kg, i.p., daily) was injected for 14 days after intracerebroventricular injection of Aβ1-42. The levels of MDA, IL-6 and TNF-α were assessed by biochemical and ELISA analysis. Morris Water Maze and open field task were used to assess the memory dysfunction and motor dysfunction, respectively. LTP were used to detect the electrophysiology changes, HNE and GFAP immunohistochemistry were used to assess the oxidative stress and glial cell activation. After Aβ1-42 injection, the levels of MDA, IL-6, and TNF-α were increased in brain tissues and hydrogen-rich saline treatment suppressed MDA, IL-6, and TNF-α concentration. Hydrogen-rich saline treatment improved Morris Water Maze and enhanced LTP in hippocampus blocked by Aβ1-42.Furthermore, hydrogen-rich saline treatment also decreased the immunoreactivitiy of HNE and GFAP in hippocampus induced by Aβ1-42. In conclusion, hydrogen-rich saline prevented Aβ-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model.

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“…The rodent HIE model has been very informative for understanding mechanisms of brain injury from peri-natal hypoxia 2 , where interventions such as hypothermia have been validated 3 . This model was initially perfected in rats and more recently adapted to mice 8 .…”

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confidence: 99%

The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia

Taniguchi¹,

Andreasson²

2008

JoVE

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Hypoxic-Ischemic Encephalopathy (HIE) is the consequence of systemic asphyxia occurring at birth. Twenty five percent of neonates with HIE develop severe and permanent neuropsychological sequelae, including mental retardation, cerebral palsy, and epilepsy. The outcomes of HIE are devastating and permanent, making it critical to identify and develop therapeutic strategies to reduce brain injury in newborns with HIE. To that end, the neonatal rat model for hypoxic-ischemic brain injury has been developed to model this human condition. The HIE model was first validated by Vannucci et al 1 and has since been extensively used to identify mechanisms of brain injury resulting from perinatal hypoxia-ischemia 2 and to test potential therapeutic interventions 3,4 . The HIE model is a two step process and involves the ligation of the left common carotid artery followed by exposure to a hypoxic environment. Cerebral blood flow (CBF) in the hemisphere ipsilateral to the ligated carotid artery does not decrease because of the collateral blood flow via the circle of Willis; however with lower oxygen tension, the CBF in the ipsilateral hemisphere decreases significantly and results in unilateral ischemic injury. The use of 2,3,5-triphenyltetrazolium chloride (TTC) to stain and identify ischemic brain tissue was originally developed for adult models of rodent cerebral ischemia 5 , and is used to evaluate the extent of cerebral infarctin at early time points up to 72 hours after the ischemic event 6 . In this video, we demonstrate the hypoxic-ischemic injury model in postnatal rat brain and the evaluation of the infarct size using TTC staining. 4. The incision is closed with cyanoacrylate adhesive (Elmers Products Inc, Columbus, OH). The incision is covered with tape and anesthesia is stopped. The pups are returned to their dam and allowed to recuperate for 1-2 hours. 5. Pups are then placed in a hypoxic chamber that contains 8% oxygen balanced with 92% nitrogen for 100 minutes at 37°C. 8% oxygen/92% nitrogen gas(Airgas, Sacramento, CA) flow via a tube into the mouse cage outfitted with a plastic cover. The cover is made to fit to the cage and has two holes of 2 cm in diameter, one of which to receive the tube connected to the 8% oxygen gas tank and another allows the gas to flowout. The chamber is placed in a water bath and is warmed up prior to use and a thermometer inside of it must register 37°C before the start of hypoxia. 6. At the end of 100 minutes of hypoxia, the pups are returned again to their dam for recovery. 7. 24 hours after the end of hypoxia, pups are euthanized by deep anesthesia with isoflurane. Brain tissue is perfused with cold normal saline, followed by a solution of cold 1% TTC in phosphate buffered saline, pH 7.4 (Sigma Chemical Co, St Louis, MO). TTC must be kept protected from light. 8. Brains are removed and cooled for 1-2 minutes on ice, and four coronal sections 3 mm apart (levels 1-4) are cut, beginning rostrally at the level of the opticchiasm and infundibulum, corresponding to the bregma 1...

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Hydrogen therapy reduces apoptosis in neonatal hypoxia–ischemia rat model

Cited by 212 publications

References 16 publications

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress

The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia

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