Hydrogen Effect on Brain

Hydrogen gas and hydrogen-rich water have been found to be effective in promoting brain health and function. Research has shown that hydrogen has antioxidant and anti-inflammatory effects in the brain, which can help protect against neurodegenerative diseases such as Alzheimer's and Parkinson's. Hydrogen gas has been shown to improve cognitive function in animal models of Alzheimer's disease. In one study, mice with Alzheimer's disease were exposed to hydrogen gas for one hour a day for four weeks. The results showed that the mice had improved cognitive function and reduced levels of oxidative stress in the brain. Hydrogen-rich water has also been found to have beneficial effects on the brain. In a study of healthy adults, drinking hydrogen-rich water for four weeks was found to improve cognitive function and reduce oxidative stress in the brain. In addition to its antioxidant and anti-inflammatory properties, hydrogen has also been found to have anti-apoptotic effects in the brain. Apoptosis is a process of programmed cell death that can occur in the brain as a result of injury or disease. By inhibiting apoptosis, hydrogen may help protect brain cells from damage and promote brain health. Overall, the evidence suggests that hydrogen gas and hydrogen-rich water may be effective in promoting brain health and function. While more research is needed to fully understand the mechanisms of action and potential benefits, these findings are promising and suggest that hydrogen may be a natural and safe approach to supporting brain health.

Imai K, Kotani T, Tsuda H, Nakano T, Ushida T, Iwase A, Nagai T, Toyokuni S, Suzumura A, Kikkawa F. Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model. Sci Rep. 2018 Jun 15;8(1):9221. doi: 10.1038/s41598-018-27626-4. PMID: 29907804; PMCID: PMC6003913.

Hong Y, Guo S, Chen S, Sun C, Zhang J, Sun X. Beneficial effect of hydrogen-rich saline on cerebral vasospasm after experimental subarachnoid hemorrhage in rats. J Neurosci Res. 2012 Aug;90(8):1670-80. doi: 10.1002/jnr.22739. Epub 2012 May 15. PMID: 22589232.

Ji X, Liu W, Xie K, Liu W, Qu Y, Chao X, Chen T, Zhou J, Fei Z. Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress. Brain Res. 2010 Oct 1;1354:196-205. doi: 10.1016/j.brainres.2010.07.038. Epub 2010 Jul 21. PMID: 20654594.

Yonamine R, Satoh Y, Kodama M, Araki Y, Kazama T. Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice. Anesthesiology. 2013 Jan;118(1):105-13. doi: 10.1097/ALN.0b013e318275146d. PMID: 23221861.

Yoshii Y, Inoue T, Uemura Y, Iwasaki Y, Yada T, Nakabeppu Y, Noda M. Complexity of Stomach-Brain Interaction Induced by Molecular Hydrogen in Parkinson's Disease Model Mice. Neurochem Res. 2017 Sep;42(9):2658-2665. doi: 10.1007/s11064-017-2281-1. Epub 2017 May 2. PMID: 28462451.

Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology. 2009 Jan;34(2):501-8. doi: 10.1038/npp.2008.95. Epub 2008 Jun 18. PMID: 18563058.

Oláh O, Tóth-Szűki V, Temesvári P, Bari F, Domoki F. Delayed neurovascular dysfunction is alleviated by hydrogen in asphyxiated newborn pigs. Neonatology. 2013;104(2):79-86. doi: 10.1159/000348445. Epub 2013 Jul 9. PMID: 23859876.

Gu Y, Huang CS, Inoue T, Yamashita T, Ishida T, Kang KM, Nakao A. Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice. J Clin Biochem Nutr. 2010 May;46(3):269-76. doi: 10.3164/jcbn.10-19. Epub 2010 Apr 23. PMID: 20490324; PMCID: PMC2872234.

Ito M, Hirayama M, Yamai K, Goto S, Ito M, Ichihara M, Ohno K. Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson's disease in rats. Med Gas Res. 2012 May 20;2(1):15. doi: 10.1186/2045-9912-2-15. PMID: 22608009; PMCID: PMC3407490.

Liu Y, Lan Q, Wang D, Chen X, Yuan J, Zhang H. [Effect of hydrogen-rich water on the CD34 expression in lesion boundary brain tissue of rats with traumatic brain injury]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 Mar;29(3):260-264. Chinese. doi: 10.3760/cma.j.issn.2095-4352.2017.03.013. PMID: 28627348.

Zhang, Y., Su, WJ., Chen, Y. et al. Effects of hydrogen-rich water on depressive-like behavior in mice. Sci Rep 6, 23742 (2016). https://doi.org/10.1038/srep23742

Chen X, Wang D, Liu Y, Yuan J, Zhang H. [Effects of hydrogen-rich water on the expression of aquaporin 1 in the cerebral cortex of rat with traumatic brain injury]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016 May;28(5):460-4. Chinese. PMID: 29923387.

Nishimaki K, Asada T, Ohsawa I, Nakajima E, Ikejima C, Yokota T, Kamimura N, Ohta S. Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment. Curr Alzheimer Res. 2018 Mar 14;15(5):482-492. doi: 10.2174/1567205014666171106145017. PMID: 29110615; PMCID: PMC5872374.

Du Z, Jia H, Liu J, Zhao X, Xu W. Effects of three hydrogen-rich liquids on hemorrhagic shock in rats. J Surg Res. 2015 Jan;193(1):377-82. doi: 10.1016/j.jss.2014.06.051. Epub 2014 Jul 3. PMID: 25130773.

Kashiwagi T, Yan H, Hamasaki T, Kinjo T, Nakamichi N, Teruya K, Kabayama S, Shirahata S. Electrochemically reduced water protects neural cells from oxidative damage. Oxid Med Cell Longev. 2014;2014:869121. doi: 10.1155/2014/869121. Epub 2014 Oct 14. PMID: 25383141; PMCID: PMC4212634.

Jiang X, Niu X, Guo Q, Dong Y, Xu J, Yin N, Qi Q, Jia Y, Gao L, He Q, Lv P. FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of vascular dementia. Behav Brain Res. 2019 Jan 1;356:98-106. doi: 10.1016/j.bbr.2018.05.023. Epub 2018 Jun 7. Erratum in: Behav Brain Res. 2019 Nov 18;374:111839. PMID: 29885845.

Chen Y, Chen H, Xie K, Liu L, Li Y, Yu Y, Wang G. H2 Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain. Inflammation. 2015 Oct;38(5):1835-46. doi: 10.1007/s10753-015-0161-x. PMID: 25820467.

Ueda Y, Kojima T, Oikawa T. Hippocampal gene network analysis suggests that coral calcium hydride may reduce accelerated senescence in mice. Nutr Res. 2011 Nov;31(11):863-72. doi: 10.1016/j.nutres.2011.09.011. PMID: 22118758.

Wu X, Li X, Liu Y, Yuan N, Li C, Kang Z, Zhang X, Xia Y, Hao Y, Tan Y. Hydrogen exerts neuroprotective effects on OGD/R damaged neurons in rat hippocampal by protecting mitochondrial function via regulating mitophagy mediated by PINK1/Parkin signaling pathway. Brain Res. 2018 Nov 1;1698:89-98. doi: 10.1016/j.brainres.2018.06.028. Epub 2018 Jun 27. PMID: 29958907.

Zhan Y, Chen C, Suzuki H, Hu Q, Zhi X, Zhang JH. Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats. Crit Care Med. 2012 Apr;40(4):1291-6. doi: 10.1097/CCM.0b013e31823da96d. PMID: 22336722; PMCID: PMC4373315.

Shi Y, Wang G, Li J, Yu W. Hydrogen gas attenuates sevoflurane neurotoxicity through inhibiting nuclear factor κ-light-chain-enhancer of activated B cells signaling and proinflammatory cytokine release in neonatal rats. Neuroreport. 2017 Dec 6;28(17):1170-1175. doi: 10.1097/WNR.0000000000000899. PMID: 28926473.

Matsuoka T, Suzuki M, Sano M, Hayashida K, Tamura T, Homma K, Fukuda K, Sasaki J. Hydrogen gas inhalation inhibits progression to the "irreversible" stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg. 2017 Sep;83(3):469-475. doi: 10.1097/TA.0000000000001620. PMID: 28640781.

Ono H, Nishijima Y, Ohta S, Sakamoto M, Kinone K, Horikosi T, Tamaki M, Takeshita H, Futatuki T, Ohishi W, Ishiguro T, Okamoto S, Ishii S, Takanami H. Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection. J Stroke Cerebrovasc Dis. 2017 Nov;26(11):2587-2594. doi: 10.1016/j.jstrokecerebrovasdis.2017.06.012. Epub 2017 Jun 29. PMID: 28669654.

Zhang L, Wang X, Tian X, Zhao W, Liu T, Feng G, Cai H, Liu J. Hydrogen has a neuroprotective effect via activation of Nrf-2/HO-1 pathway in ischemia reperfusion rat. Int J Clin Exp Med 2016;9(6):10521-10528.

Takeuchi S, Nagatani K, Otani N, Nawashiro H, Sugawara T, Wada K, Mori K. Hydrogen improves neurological function through attenuation of blood-brain barrier disruption in spontaneously hypertensive stroke-prone rats. BMC Neurosci. 2015 Apr 20;16:22. doi: 10.1186/s12868-015-0165-3. PMID: 25925889; PMCID: PMC4411925.

Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Tanaka Y, Nakabeppu Y, Noda M. Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. PLoS One. 2009 Sep 30;4(9):e7247. doi: 10.1371/journal.pone.0007247. PMID: 19789628; PMCID: PMC2747267.

Manaenko A, Lekic T, Ma Q, Zhang JH, Tang J. Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice. Crit Care Med. 2013 May;41(5):1266-75. doi: 10.1097/CCM.0b013e31827711c9. PMID: 23388512; PMCID: PMC3630247.

Huang JL, Liu WW, Sun XJ. Hydrogen inhalation improves mouse neurological outcomes after cerebral ischemia/reperfusion independent of anti-necroptosis. Med Gas Res. 2018 Apr 18;8(1):1-5. doi: 10.4103/2045-9912.229596. PMID: 29770189; PMCID: PMC5937297.

Manaenko A, Lekic T, Ma Q, Ostrowski RP, Zhang JH, Tang J. Hydrogen inhalation is neuroprotective and improves functional outcomes in mice after intracerebral hemorrhage. Acta Neurochir Suppl. 2011;111:179-83. doi: 10.1007/978-3-7091-0693-8_30. PMID: 21725752; PMCID: PMC3569058.

Eckermann JM, Chen W, Jadhav V, Hsu FP, Colohan AR, Tang J, Zhang JH. Hydrogen is neuroprotective against surgically induced brain injury. Med Gas Res. 2011 May 18;1(1):7. doi: 10.1186/2045-9912-1-7. PMID: 22146427; PMCID: PMC3231979.

Domoki F, Oláh O, Zimmermann A, Németh I, Tóth-Szuki V, Hugyecz M, Temesvári P, Bari F. Hydrogen is neuroprotective and preserves cerebrovascular reactivity in asphyxiated newborn pigs. Pediatr Res. 2010 Nov;68(5):387-92. doi: 10.1203/PDR.0b013e3181f2e81c. PMID: 20657346.

Mei K, Zhao S, Qian L, Li B, Ni J, Cai J. Hydrogen protects rats from dermatitis caused by local radiation. J Dermatolog Treat. 2014 Apr;25(2):182-8. doi: 10.3109/09546634.2012.762639. Epub 2013 May 31. PMID: 23273331.

Wang W, Li Y, Ren J, Xia F, Li J, Zhang Z. Hydrogen rich saline reduces immune-mediated brain injury in rats with acute carbon monoxide poisoning. Neurol Res. 2012 Dec;34(10):1007-15. doi: 10.1179/1743132812Y.0000000106. PMID: 23146304.

Li D, Ai Y. Hydrogen saline suppresses neuronal cell apoptosis and inhibits the p38 mitogen‑activated protein kinase‑caspase‑3 signaling pathway following cerebral ischemia‑reperfusion injury. Mol Med Rep. 2017 Oct;16(4):5321-5325. doi: 10.3892/mmr.2017.7294. Epub 2017 Aug 21. PMID: 28849153; PMCID: PMC5647063.

Hugyecz M, Mracskó E, Hertelendy P, Farkas E, Domoki F, Bari F. Hydrogen supplemented air inhalation reduces changes of prooxidant enzyme and gap junction protein levels after transient global cerebral ischemia in the rat hippocampus. Brain Res. 2011 Aug 2;1404:31-8. doi: 10.1016/j.brainres.2011.05.068. Epub 2011 Jun 12. PMID: 21718970.

Wei R, Zhang R, Xie Y, Shen L, Chen F. Hydrogen Suppresses Hypoxia/Reoxygenation-Induced Cell Death in Hippocampal Neurons Through Reducing Oxidative Stress. Cell Physiol Biochem. 2015;36(2):585-98. doi: 10.1159/000430122. PMID: 25997722.

Yang L, Li D, Chen S. Hydrogen water reduces NSE, IL-6, and TNF-α levels in hypoxic-ischemic encephalopathy. Open Med (Wars). 2016 Oct 21;11(1):399-406. doi: 10.1515/med-2016-0072. PMID: 28352827; PMCID: PMC5329859.

Ueda Y, Nakajima A, Oikawa T. Hydrogen-related enhancement of in vivo antioxidant ability in the brain of rats fed coral calcium hydride. Neurochem Res. 2010 Oct;35(10):1510-5. doi: 10.1007/s11064-010-0204-5. Epub 2010 Jul 22. PMID: 20652633.

Sato Y, Kajiyama S, Amano A, Kondo Y, Sasaki T, Handa S, Takahashi R, Fukui M, Hasegawa G, Nakamura N, Fujinawa H, Mori T, Ohta M, Obayashi H, Maruyama N, Ishigami A. Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem Biophys Res Commun. 2008 Oct 24;375(3):346-50. doi: 10.1016/j.bbrc.2008.08.020. Epub 2008 Aug 14. PMID: 18706888.

Wang H, Huo X, Chen H, Li B, Liu J, Ma W, Wang X, Xie K, Yu Y, Shi K. Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model. Biomed Res Int. 2018 May 17;2018:4670834. doi: 10.1155/2018/4670834. PMID: 29888265; PMCID: PMC5985079.

Zhuang Z, Zhou ML, You WC, Zhu L, Ma CY, Sun XJ, Shi JX. Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits. BMC Neurosci. 2012 May 15;13:47. doi: 10.1186/1471-2202-13-47. PMID: 22587664; PMCID: PMC3436733.

Shao A, Wu H, Hong Y, Tu S, Sun X, Wu Q, Zhao Q, Zhang J, Sheng J. Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome. Mol Neurobiol. 2016 Jul;53(5):3462-3476. doi: 10.1007/s12035-015-9242-y. Epub 2015 Jun 20. PMID: 26091790.

Wen D, Zhao P, Hui R, Wang J, Shen Q, Gong M, Guo H, Cong B, Ma C. Hydrogen-rich saline attenuates anxiety-like behaviors in morphine-withdrawn mice. Neuropharmacology. 2017 May 15;118:199-208. doi: 10.1016/j.neuropharm.2017.03.029. Epub 2017 Mar 28. PMID: 28359771.

Ma H, Chen H, Dong A, Wang Y, Bian Y, Xie K. [Hydrogen-rich saline attenuates hyperalgesia and reduces cytokines in rats with post-herpetic neuralgia via activating autophagy]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017 Feb;33(2):155-8. Chinese. PMID: 29762002.

Li C, Hou L, Chen D, Lin F, Chang T, Li M, Zhang L, Niu X, Wang H, Fu S, Zheng J. Hydrogen-rich saline attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. Am J Transl Res. 2017 Mar 15;9(3):1162-1172. PMID: 28386342; PMCID: PMC5376007.

Cui Y, Zhang H, Ji M, Jia M, Chen H, Yang J, Duan M. Hydrogen-rich saline attenuates neuronal ischemia-reperfusion injury by protecting mitochondrial function in rats. J of Surgical Research. 2014 December;192(2);564-572. https://doi.org/10.1016/j.jss.2014.05.060

Zhang L, Shu R, Wang C, Wang H, Li N, Wang G. Hydrogen-rich saline controls remifentanil-induced hypernociception and NMDA receptor NR1 subunit membrane trafficking through GSK-3β in the DRG in rats. Brain Res Bull. 2014 Jul;106:47-55. doi: 10.1016/j.brainresbull.2014.05.005. Epub 2014 Jun 18. PMID: 24951883.

Li J, Wang C, Zhang JH, Cai JM, Cao YP, Sun XJ. Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Res. 2010 Apr 30;1328:152-61. doi: 10.1016/j.brainres.2010.02.046. Epub 2010 Feb 19. PMID: 20171955.

Shen L, Wang J, Liu K, Wang C, Wang C, Wu H, Sun Q, Sun X, Jing H. Hydrogen-rich saline is cerebroprotective in a rat model of deep hypothermic circulatory arrest. Neurochem Res. 2011 Aug;36(8):1501-11. doi: 10.1007/s11064-011-0476-4. Epub 2011 Apr 22. PMID: 21512745.

Bai X, Liu S, Yuan L, Xie Y, Li T, Wang L, Wang X, Zhang T, Qin S, Song G, Ge L, Wang Z. Hydrogen-rich saline mediates neuroprotection through the regulation of endoplasmic reticulum stress and autophagy under hypoxia-ischemia neonatal brain injury in mice. Brain Res. 2016 Sep 1;1646:410-417. doi: 10.1016/j.brainres.2016.06.020. Epub 2016 Jun 15. PMID: 27317636.

Feng Y, Wang R, Xu J, Sun J, Xu T, Gu Q, Wu X. Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats. Curr Eye Res. 2013 Mar;38(3):396-404. doi: 10.3109/02713683.2012.748919. Epub 2012 Dec 19. PMID: 23252792.

Zhang YG, Sheng QS, Wang ZJ, Lv LI, Zhao W, Chen JM, Xu H. Hydrogen-rich saline promotes motor functional recovery following peripheral nerve autografting in rats. Exp Ther Med. 2015 Aug;10(2):727-732. doi: 10.3892/etm.2015.2518. Epub 2015 May 26. PMID: 26622383; PMCID: PMC4508974.

Hou Z, Luo W, Sun X, Hao S, Zhang Y, Xu F, Wang Z, Liu B. Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Res Bull. 2012 Sep 1;88(6):560-5. doi: 10.1016/j.brainresbull.2012.06.006. Epub 2012 Jun 26. PMID: 22742936.

Sun Q, Cai J, Zhou J, Tao H, Zhang JH, Zhang W, Sun XJ. Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon monoxide toxicity. Crit Care Med. 2011 Apr;39(4):765-9. doi: 10.1097/CCM.0b013e318206bf44. PMID: 21200321.

Wang C, Li J, Liu Q, Yang R, Zhang JH, Cao YP, Sun XJ. Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease. Neurosci Lett. 2011 Mar 17;491(2):127-32. doi: 10.1016/j.neulet.2011.01.022. Epub 2011 Jan 14. PMID: 21238541.

Zhou J, Chen Y, Huang GQ, Li J, Wu GM, Liu L, Bai YP, Wang J. Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture. J Surg Res. 2012 Nov;178(1):390-400. doi: 10.1016/j.jss.2012.01.041. Epub 2012 Apr 1. PMID: 22482765.

Lin CL, Huang WN, Li HH, Huang CN, Hsieh S, Lai C, Lu FJ. Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells. Chem Biol Interact. 2015 Oct 5;240:12-21. doi: 10.1016/j.cbi.2015.07.013. Epub 2015 Aug 10. PMID: 26271894.

Tian R, Hou Z, Hao S, Wu W, Mao X, Tao X, Lu T, Liu B. Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats. Brain Res. 2016 Apr 15;1637:1-13. doi: 10.1016/j.brainres.2016.01.029. Epub 2016 Jan 26. PMID: 26826009.

Yuan J, Wang D, Liu Y, Chen X, Zhang H, Shen F, Liu X, Fu J. Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway. J Surg Res. 2018 Aug;228:238-246. doi: 10.1016/j.jss.2018.03.024. Epub 2018 Apr 11. PMID: 29907217.

Mizuno K, Sasaki AT, Ebisu K, Tajima K, Kajimoto O, Nojima J, Kuratsune H, Hori H, Watanabe Y. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med Gas Res. 2018 Jan 22;7(4):247-255. doi: 10.4103/2045-9912.222448. PMID: 29497485; PMCID: PMC5806445.

Hou C, Peng Y, Qin C, Fan F, Liu J, Long J. Hydrogen-rich water improves cognitive impairment gender-dependently in APP/PS1 mice without affecting Aβ clearance. Free Radic Res. 2018 Dec;52(11-12):1311-1322. doi: 10.1080/10715762.2018.1460749. Epub 2018 Apr 23. PMID: 29683360.

Zhao M, Liu MD, Pu YY, Wang D, Xie Y, Xue GC, Jiang Y, Yang QQ, Sun XJ, Cao L. Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2016 May 15;294:6-13. doi: 10.1016/j.jneuroim.2016.03.006. Epub 2016 Mar 14. PMID: 27138092.

Han L, Tian R, Yan H, Pei L, Hou Z, Hao S, Li YV, Tian Q, Liu B, Zhang Q. Hydrogen-rich water protects against ischemic brain injury in rats by regulating calcium buffering proteins. Brain Res. 2015 Jul 30;1615:129-138. doi: 10.1016/j.brainres.2015.04.038. Epub 2015 Apr 25. PMID: 25920370.

He Y, Zhang B, Chen Y, Jin Q, Wu J, Yan F, Zheng H. Image-Guided Hydrogen Gas Delivery for Protection from Myocardial Ischemia-Reperfusion Injury via Microbubbles. ACS Appl Mater Interfaces. 2017 Jun 28;9(25):21190-21199. doi: 10.1021/acsami.7b05346. Epub 2017 Jun 16. PMID: 28557412.

Ono H, Nishijima Y, Adachi N, Tachibana S, Chitoku S, Mukaihara S, Sakamoto M, Kudo Y, Nakazawa J, Kaneko K, Nawashiro H. Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study. Med Gas Res. 2011 Jun 7;1(1):12. doi: 10.1186/2045-9912-1-12. PMID: 22146068; PMCID: PMC3231971.

Liu L, Xie K, Chen H, Dong X, Li Y, Yu Y, Wang G, Yu Y. Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Res. 2014 Nov 17;1589:78-92. doi: 10.1016/j.brainres.2014.09.030. Epub 2014 Sep 22. PMID: 25251596.

Cui J, Chen X, Zhai X, Shi D, Zhang R, Zhi X, Li X, Gu Z, Cao L, Weng W, Zhang J, Wang L, Sun X, Ji F, Hou J, Su J. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use. Neuroscience. 2016 Oct 29;335:232-41. doi: 10.1016/j.neuroscience.2016.08.021. Epub 2016 Aug 21. Erratum in: Neuroscience. 2020 Nov 10;448:337-338. PMID: 27555551.

Mano Y, Kotani T, Ito M, Nagai T, Ichinohashi Y, Yamada K, Ohno K, Kikkawa F, Toyokuni S. Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion. Free Radic Biol Med. 2014 Apr;69:324-30. doi: 10.1016/j.freeradbiomed.2014.01.037. Epub 2014 Feb 6. PMID: 24509162.

Nakano T, Kotani T, Mano Y, Tsuda H, Imai K, Ushida T, Li H, Miki R, Sumigama S, Sato Y, Iwase A, Hirakawa A, Asai M, Toyokuni S, Kikkawa F. Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury. J Clin Biochem Nutr. 2015 Nov;57(3):178-82. doi: 10.3164/jcbn.15-90. Epub 2015 Oct 21. Erratum in: J Clin Biochem Nutr. 2016 Jul;59(1):78. PMID: 26566302; PMCID: PMC4639595.

Nemeth J, Toth-Szuki V, Varga V, Kovacs V, Remzso G, Domoki F. Molecular hydrogen affords neuroprotection in a translational piglet model of hypoxic-ischemic encephalopathy. J Physiol Pharmacol. 2016 Oct;67(5):677-689. PMID: 28011948.

Varga V, Németh J, Oláh O, Tóth-Szűki V, Kovács V, Remzső G, Domoki F. Molecular hydrogen alleviates asphyxia-induced neuronal cyclooxygenase-2 expression in newborn pigs. Acta Pharmacol Sin. 2018 Aug;39(8):1273-1283. doi: 10.1038/aps.2017.148. Epub 2018 Mar 22. PMID: 29565041; PMCID: PMC6289359.

Dohi K, Kraemer BC, Erickson MA, McMillan PJ, Kovac A, Flachbartova Z, Hansen KM, Shah GN, Sheibani N, Salameh T, Banks WA. Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury. PLoS One. 2014 Sep 24;9(9):e108034. doi: 10.1371/journal.pone.0108034. PMID: 25251220; PMCID: PMC4176020.

Gao Q, Song H, Wang XT, Liang Y, Xi YJ, Gao Y, Guo QJ, LeBaron T, Luo YX, Li SC, Yin X, Shi HS, Ma YX. Molecular hydrogen increases resilience to stress in mice. Sci Rep. 2017 Aug 29;7(1):9625. doi: 10.1038/s41598-017-10362-6. PMID: 28852144; PMCID: PMC5575246.

Fu Y, Ito M, Fujita Y, Ito M, Ichihara M, Masuda A, Suzuki Y, Maesawa S, Kajita Y, Hirayama M, Ohsawa I, Ohta S, Ohno K. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease. Neurosci Lett. 2009 Apr 3;453(2):81-5. doi: 10.1016/j.neulet.2009.02.016. Epub 2009 Feb 12. PMID: 19356598.

Satoh Y, Araki Y, Kashitani M, Nishii K, Kobayashi Y, Fujita M, Suzuki S, Morimoto Y, Tokuno S, Tsumatori G, Yamamoto T, Saitoh D, Ishizuka T. Molecular Hydrogen Prevents Social Deficits and Depression-Like Behaviors Induced by Low-Intensity Blast in Mice. J Neuropathol Exp Neurol. 2018 Sep 1;77(9):827-836. doi: 10.1093/jnen/nly060. PMID: 30053086.

Murakami Y, Ito M, Ohsawa I. Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis. PLoS One. 2017 May 3;12(5):e0176992. doi: 10.1371/journal.pone.0176992. PMID: 28467497; PMCID: PMC5415102.

Spulber S, Edoff K, Hong L, Morisawa S, Shirahata S, Ceccatelli S. Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLoS One. 2012;7(7):e42078. doi: 10.1371/journal.pone.0042078. Epub 2012 Jul 31. PMID: 22860058; PMCID: PMC3409143.

Liu FT, Xu SM, Xiang ZH, Li XN, Li J, Yuan HB, Sun XJ. Molecular hydrogen suppresses reactive astrogliosis related to oxidative injury during spinal cord injury in rats. CNS Neurosci Ther. 2014 Aug;20(8):778-86. doi: 10.1111/cns.12258. Epub 2014 Mar 31. PMID: 24685114; PMCID: PMC6493038.

Takaenoki Y, Satoh Y, Araki Y, Kodama M, Yonamine R, Yufune S, Kazama T. Neonatal exposure to sevoflurane in mice causes deficits in maternal behavior later in adulthood. Anesthesiology. 2014 Feb;120(2):403-15. doi: 10.1097/ALN.0000435846.28299.e7. PMID: 24061597.

Hong Y, Shao A, Wang J, Chen S, Wu H, McBride DW, Wu Q, Sun X, Zhang J. Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3β signaling pathway. PLoS One. 2014 Apr 24;9(4):e96212. doi: 10.1371/journal.pone.0096212. PMID: 24763696; PMCID: PMC3999200.

Shen MH, Cai JM, Sun Q, Zhang DW, Huo ZL, He J, Sun XJ. Neuroprotective effect of hydrogen-rich saline in acute carbon monoxide poisoning. CNS Neurosci Ther. 2013 May;19(5):361-3. doi: 10.1111/cns.12094. PMID: 23607699; PMCID: PMC6493549.

Li Q, Yu P, Zeng Q, Luo B, Cai S, Hui K, Yu G, Zhu C, Chen X, Duan M, Sun X. Neuroprotective Effect of Hydrogen-Rich Saline in Global Cerebral Ischemia/Reperfusion Rats: Up-Regulated Tregs and Down-Regulated miR-21, miR-210 and NF-κB Expression. Neurochem Res. 2016 Oct;41(10):2655-2665. doi: 10.1007/s11064-016-1978-x. Epub 2016 Jul 7. PMID: 27386874; PMCID: PMC5065604.

Kuroki Ch, Tokumaru O, Ogata K, Koga H, Yokoi I. Neuroprotective effects of hydrogen gas on brain in three types of stress models: α 31P-NMR study. Neuroscience Research. 2009 December;65. http://dx.doi.org/10.1016/j.neures.2009.09.590

Choi KS, Kim HJ, Do SH, Hwang SJ, Yi HJ. Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model. Brain Res Bull. 2018 Sep;142:122-128. doi: 10.1016/j.brainresbull.2018.07.006. Epub 2018 Jul 18. PMID: 30016724.

Zhuang Z, Sun XJ, Zhang X, Liu HD, You WC, Ma CY, Zhu L, Zhou ML, Shi JX. Nuclear factor-κB/Bcl-XL pathway is involved in the protective effect of hydrogen-rich saline on the brain following experimental subarachnoid hemorrhage in rabbits. J Neurosci Res. 2013 Dec;91(12):1599-608. doi: 10.1002/jnr.23281. Epub 2013 Sep 16. PMID: 24105634.

Matsumoto A, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H. Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice. Sci Rep. 2013 Nov 20;3:3273. doi: 10.1038/srep03273. PMID: 24253616; PMCID: PMC4070541.

Wang T, Zhao L, Liu M, Xie F, Ma X, Zhao P, Liu Y, Li J, Wang M, Yang Z, Zhang Y. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats. Toxicol Appl Pharmacol. 2014 Oct 1;280(1):169-76. doi: 10.1016/j.taap.2014.06.011. Epub 2014 Jun 24. PMID: 24967689.

Tomura S, Fujii K, Ueno H, Tomiyama A, Otani N, Osada H, Wada K, Mori K. Physiological effects of combination therapy of intracisternal infusion of magnesium sulfate solution and intravenous injection of hydrogen-enriched fluid in the rat. J of the National Defence Medical College. 2014 January;39(2);96-102.

Yoritaka A, Takanashi M, Hirayama M, Nakahara T, Ohta S, Hattori N. Pilot study of H₂ therapy in Parkinson's disease: a randomized double-blind placebo-controlled trial. Mov Disord. 2013 Jun;28(6):836-9. doi: 10.1002/mds.25375. Epub 2013 Feb 11. PMID: 23400965.

Yoneda T, Tomofuji T, Kunitomo M, Ekuni D, Irie K, Azuma T, Machida T, Miyai H, Fujimori K, Morita M. Preventive Effects of Drinking Hydrogen-Rich Water on Gingival Oxidative Stress and Alveolar Bone Resorption in Rats Fed a High-Fat Diet. Nutrients. 2017 Jan 13;9(1):64. doi: 10.3390/nu9010064. PMID: 28098768; PMCID: PMC5295108.

Yu Y, Ma X, Yang T, Li B, Xie K, Liu D, Wang G, Yu Y. Protective effect of hydrogen-rich medium against high glucose-induced apoptosis of Schwann cells in vitro. Mol Med Rep. 2015 Sep;12(3):3986-3992. doi: 10.3892/mmr.2015.3874. Epub 2015 Jun 2. PMID: 26035067.

Liu W, Chen O, Chen C, Wu B, Tang J, Zhang JH. Protective effects of hydrogen on fetal brain injury during maternal hypoxia. Acta Neurochir Suppl. 2011;111:307-11. doi: 10.1007/978-3-7091-0693-8_51. PMID: 21725773; PMCID: PMC3569076.

Ji X, Tian Y, Xie K, Liu W, Qu Y, Fei Z. Protective effects of hydrogen-rich saline in a rat model of traumatic brain injury via reducing oxidative stress. J Surg Res. 2012 Nov;178(1):e9-16. doi: 10.1016/j.jss.2011.12.038. Epub 2012 Mar 22. PMID: 22475349.

Jelic V, Kivipelto M, Winblad B. Clinical trials in mild cognitive impairment: lessons for the future. J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):429-38. doi: 10.1136/jnnp.2005.072926. Epub 2005 Nov 23. Erratum in: J Neurol Neurosurg Psychiatry. 2006 Jul;77(7):892. PMID: 16306154; PMCID: PMC2077499.

Hong Y, Chen S, Zhang JM. [Research advances on hydrogen therapy in nervous system diseases]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2010 Nov;39(6):638-43. Chinese. doi: 10.3785/j.issn.1008-9292.2010.06.015. PMID: 21166060.

Nagatani K, Nawashiro H, Takeuchi S, Tomura S, Otani N, Osada H, Wada K, Katoh H, Tsuzuki N, Mori K. Safety of intravenous administration of hydrogen-enriched fluid in patients with acute cerebral ischemia: initial clinical studies. Med Gas Res. 2013 Jun 25;3:13. doi: 10.1186/2045-9912-3-13. PMID: 23799921; PMCID: PMC3694409.

Kashiwagi T, Hamasaki T, Kabayama S, Takaki M, Teruya K, Katakura Y, Otubo K, Morisawa S, Shirahata S. Suppression of Oxidative Stress-Induced Apoptosis of Neuronal Cells by Electrolyzed-Reduced Water. Animal Cell Tehnology Meets Genomics. 2005; 257-260.

Yan H, Kashiwaki T, Hamasaki T, Kinjo T, Teruya K, Kabayama S, Shirahata S. The neuroprotective effects of electrolyzed reduced water and its model water containing molecular hydrogen and Pt nanoparticles. BMC Proc. 2011 Nov 22;5 Suppl 8(Suppl 8):P69. doi: 10.1186/1753-6561-5-S8-P69. PMID: 22373490; PMCID: PMC3285010.

Huang G, Zhou J, Zhan W, Xiong Y, Hu C, Li X, Li X, Li Y, Liao X. The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest. Resuscitation. 2013 May;84(5):690-5. doi: 10.1016/j.resuscitation.2012.10.018. Epub 2012 Oct 27. PMID: 23108240.

Wang X, Zhang L, Zhao W, Liu T. The protective effects of hydrogen on HO-1 expression in the brainafter focal cerebral ischemia reperfusion in rats. Turk J Med Sci. 2016 Nov 17;46(5):1534-1539. doi: 10.3906/sag-1502-3. PMID: 27966325.

Du Z, Liu J, Jia H, Xu W, Zhao X. Three hydrogen-rich solutions protect against intestinal injury in uncontrolled hemorrhagic shock. Int J Clin Exp Med. 2015 May 15;8(5):7620-6. PMID: 26221308; PMCID: PMC4509253.

Zhang Y, Li H, Yang C, Fan DF, Guo DZ, Hu HJ, Meng XE, Pan SY. Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis. Neurochem Res. 2016 Apr;41(4):770-8. doi: 10.1007/s11064-015-1750-7. Epub 2015 Nov 4. PMID: 26537817.