Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model

Choi, Kyu Sun; Kim, Hanjun; Hee, Sun; Hwang, Se Jin; Yi, Hyeong Joong

doi:10.1016/j.brainresbull.2018.07.006

Cited by 26 publications

(17 citation statements)

References 27 publications

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“…These results suggest that BDNF/TrkB signaling is involved in regulating neuronal survival after ICH. Consistent with our findings, several preclinical studies, using various therapeutic interventions, such as endothelial progenitor cells transplantation [36], hydrogen inhalation [15], and rehabilitative training [37], have reported BDNF signaling as a potential therapeutic target following ICH. Together with previous reports, our findings support the speculation that BDNF-TrkB signaling participates in the pathophysiological process of ICH.…”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, activated Akt blocks Fas ligand transcription by phosphorylating FOXO, thereby inhibiting ligand-induced extrinsic apoptosis [14]. However, evidence shows that ICH induces a decrease in BDNF expression [15], implying that this endogenous protective response to counteract neuronal damage is often attenuated. In view of the role of the BDNF-TrkB signaling in neuronal survival, targeting the BDNF-TrkB system may be a therapeutic strategy to reduce ICH-induced brain injury.…”

Section: Introductionmentioning

confidence: 99%

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Activation of TrkB/Akt signaling by a TrkB receptor agonist improves long-term histological and functional outcomes in experimental intracerebral hemorrhage

Chen

Hung

et al. 2019

J Biomed Sci

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Background Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades that contribute to secondary neuronal damage. Tropomyosin-related kinase receptor B (TrkB) signaling plays a crucial role in promoting neuronal survival following brain damage. Methods The present study investigated the protective effects and underlying mechanisms of TrkB activation by the specific TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), in a model of collagenase-induced ICH and in neuronal cultures. Mice subjected to collagenase-induced ICH were intraperitoneally injected with either 7,8-DHF or vehicle 10 min after ICH and, subsequently, daily for 3 days. Behavioral studies, brain edema measurement, and histological analysis were conducted. Levels of TrkB signaling-related molecules and apoptosis-related proteins were analyzed by western blots. Results Treatment with 20 mg/kg 7,8-DHF significantly improved functional recovery and reduced brain damage up to 28 days post-ICH. Reduction in neuronal death, apoptosis, and brain edema were also observed in response to 7,8-DHF treatment at 3 days post-ICH. These changes were accompanied by a significant increase in the phosphorylation of TrkB and Akt (Ser473/Thr308) at 1 and 3 days, but had no effect on Erk 44/42 phosphorylation. 7,8-DHF also enhanced the phosphorylation of Ask-1 Ser967 and FOXO-1, downstream targets of Akt at 1 and 3 days. Moreover, 7,8-DHF increased brain-derived neurotrophic factor levels at 1 day. In primary cultured neurons stimulated with hemin, 7,8-DHF promoted survival and reduced apoptosis. Furthermore, delaying the administration of 7,8-DHF to 3 h post-ICH reduced brain tissue damage and neuronal death. Conclusions Our findings demonstrate that the activation of TrkB signaling by 7,8-DHF protects against ICH via the Akt, but not the Erk, pathway. These data provide new insights into the role of TrkB signaling deficit in the pathophysiology of ICH and highlight TrkB/Akt as possible therapeutic targets in this disease.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Activation of TrkB/Akt signaling by a TrkB receptor agonist improves long-term histological and functional outcomes in experimental intracerebral hemorrhage

Chen

Hung

et al. 2019

J Biomed Sci

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“…These results suggest that the reduction in inflammatory response induced by MFG-E8 treatment is associated with increased angiogenesis and neuronal proliferation in the subacute cerebral infarction model. The findings are consistent with those in studies using a similar experimental model of stroke 6,7,10,15,23,25) , which indicate the potential of MFG-E8 as a neuroprotective agent to help improve prognosis after acute cerebral infarction.…”

Section: Discussionsupporting

confidence: 89%

Milk Fat Globule-Epidermal Growth Factor VIII Ameliorates Brain Injury in the Subacute Phase of Cerebral Ischemia in an Animal Model

Choi

Kang

Han

et al. 2020

J Korean Neurosurg Soc

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Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU-and DCX-positive cells in the subventricular zone in the MFG-E8treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.

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“…by ohsawa et al (27). Thereafter, many studies have demonstrated the therapeutic effects of low concentrations of H 2 inhalation on different diseases (33)(34)(35). in comparison with other methods, inhalation of H 2 gas could provide more H 2 , especially at high concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effects of the inhalation of low concentrations (2 and 4%) of H 2 gas against ischemia/reperfusion injuries were first described by Ohsawa et al ( 27 ). Thereafter, many studies have demonstrated the therapeutic effects of low concentrations of H 2 inhalation on different diseases ( 33 – 35 ). In comparison with other methods, inhalation of H 2 gas could provide more H 2 , especially at high concentrations.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats

Liu¹,

Xue²,

Zhang³

et al. 2020

Mol Med Rep

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Hydrogen exhibits therapeutic and preventive effects against various diseases. The present study investigated the potential protective effect and dose-dependent manner of hydrogen inhalation on high fat and fructose diet (HFFd)-induced nonalcoholic fatty liver disease (naFld) in Sprague-dawley rats. rats were randomly divided into four groups: i) control group, regular diet/air inhalation; ii) model group, HFFd/air inhalation; iii) low hydrogen group, HFFd/4% hydrogen inhalation; and iv) high hydrogen group, HFFd/67% hydrogen inhalation. after a 10-week experiment, hydrogen inhalation ameliorated weight gain, abdominal fat index, liver index and body mass index of rats fed with HFFd and lowered the total area under the curve in an oral glucose tolerance test. Hydrogen inhalation also ameliorated the increase in liver lipid content and alanine transaminase and aspartate transaminase activities. liver histopathologic changes evaluated with hematoxylin and eosin as well as oil red o staining revealed lower lipid deposition in hydrogen inhalation groups, consistent with the decrease in the expression of the lipid synthesis gene SREBP-1c. The majority of the indicators were affected following treatment with hydrogen in a dose-dependent manner. in conclusion, hydrogen inhalation may play a protective role by influencing the general state, lipid metabolism parameters, liver histology and liver function indicators in the rat model of metabolic syndrome with naFld.

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Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model

Cited by 26 publications

References 27 publications

Activation of TrkB/Akt signaling by a TrkB receptor agonist improves long-term histological and functional outcomes in experimental intracerebral hemorrhage

Activation of TrkB/Akt signaling by a TrkB receptor agonist improves long-term histological and functional outcomes in experimental intracerebral hemorrhage

Milk Fat Globule-Epidermal Growth Factor VIII Ameliorates Brain Injury in the Subacute Phase of Cerebral Ischemia in an Animal Model

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats

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