ArticlePloS one2014
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.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 47 papers.
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47 citing papers in PubMed, 100 citations in OpenAlex.
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- The Landscape of Smart Biomaterial-Based Hydrogen Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
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- Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies.Journal of neuroinflammation · 2024Review
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- Effects of hydrogen-rich saline in neuroinflammation and mitochondrial dysfunction in rat model of sepsis-associated encephalopathy.Journal of translational medicine · 2022Article
- Exploration of a Brain-Liver-Communication-Related Mechanism Involved in the Experimental Perimenopausal Depression Rat Model using Chaihu-Shugan-San.Neurochemical research · 2022Article
- The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.Fluids and barriers of the CNS · 2022Review
- Melatonin as a Potential Neuroprotectant: Mechanisms in Subarachnoid Hemorrhage-Induced Early Brain Injury.Frontiers in aging neuroscience · 2022Review
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- Neuroprotective Effects of Molecular Hydrogen: A Critical Review.Neuroscience bulletin · 2021Review
- Molecular and Cellular Mechanisms Associated with Effects of Molecular Hydrogen in Cardiovascular and Central Nervous Systems.Antioxidants (Basel, Switzerland) · 2020Review
- Calpastatin peptide attenuates early brain injury following experimental subarachnoid hemorrhage.Experimental and therapeutic medicine · 2020Article
- Exogenous brain-derived neurotrophic factor attenuates neuronal apoptosis and neurological deficits after subarachnoid hemorrhage in rats.Experimental and therapeutic medicine · 2019Article
- UPLC-QTOF/MS-Based Metabolomics Reveals the Protective Mechanism of Hydrogen on Mice with Ischemic Stroke.Neurochemical research · 2019Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundsEarly brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Neuronal apoptosis is involved in the pathological process of EBI. Hydrogen can inhibit neuronal apoptosis and attenuate EBI following SAH. However, the molecular mechanism underlying hydrogen-mediated anti-apoptotic effects in SAH has not been elucidated. In the present study, we aimed to evaluate whether hydrogen alleviates EBI after SAH, specifically neuronal apoptosis, partially via the Akt/GSK3β signaling pathway.
methodsSprague-Dawley rats (n = 85) were randomly divided into the following groups: sham group (n = 17), SAH group (n = 17), SAH + saline group (n = 17), SAH + hydrogen-rich saline (HS) group (n = 17) and SAH + HS + Ly294002 (n = 17) group. HS or an equal volume of physiological saline was administered immediately after surgery and repeated 8 hours later. The PI3K inhibitor, Ly294002, was applied to manipulate the proposed pathway. Neurological score and SAH grade were assessed at 24 hours after SAH. Western blot was used for the quantification of Akt, pAkt, GSK3β, pGSK3β, Bcl-2, Bax and cleaved caspase-3 proteins. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining and NeuN, and quantified by apoptosis index. Immunohistochemistry and immunofluorescent double-labeling staining was performed to clarify the relationships between neuronal apoptosis and pAkt or pGSK3β.
resultsHS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. The levels of pAkt and pGSK3β, mainly expressed in neurons, were markedly up-regulated. Additionally, Bcl-2 was significantly increased while Bax and cleaved caspase-3 was decreased by HS treatment. Double staining of pAkt and TUNEL showed few colocalization of pAkt-positive cells and TUNEL-positive cells. The inhibitor of PI3K, Ly294002, suppressed the beneficial effects of HS.
conclusionsHS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway.
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