Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats
Zhan Y, Chen C, Suzuki H, Hu Q, Zhi X, Zhang JH. · Critical Care Medicine. 2012;40(4):1291-1296.
Study at a glance
Preclinical
One hundred thirty-seven adult male Sprague-Dawley rats in an endovascular-perforation subarachnoid-hemorrhage model.
A two-hour chamber exposure began one hour after SAH using premixed 2.9% H₂, 20% O₂ and balance nitrogen. · Total gas flow was 8 L/min for the first five minutes, then 6 L/min. Therefore H₂ flow was 232 mL/min initially and 174 mL/min during maintenance; O₂ flow was 1,600 mL/min initially and 1,200 mL/min during maintenance. These are direct calculations from the source's reported composition and total flows.
One two-hour exposure starting one hour after hemorrhage; outcomes at 24 and 72 hours.
At 24 hours H₂ reduced edema, barrier leakage, apoptosis and oxidative markers and improved neurological score. Mortality was not significantly different (15.3% vs 9.8%); body weight was unchanged; neurological improvement and edema reduction were absent at 72 hours; Evans-blue reduction at 24 hours was absent in cerebellum and brainstem. The authors described the benefit as transient.
Single short exposure in a rat model, severity-based exclusions, many surrogate endpoints, no durable benefit at 72 hours and no human participants. NIH grant support was reported; authors disclosed no potential conflicts.
What kind of evidence is this?
Preclinical
Randomized three-group controlled rat subarachnoid-hemorrhage experiment
Other neurological conditions
Inhaled H₂
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
One hundred thirty-seven adult male Sprague-Dawley rats in an endovascular-perforation subarachnoid-hemorrhage model.
137 rats randomized to sham n=27, SAH n=59 or SAH plus H₂ n=51. Moderate-SAH animals were retained for most outcome analyses; mild and severe cases were excluded according to prespecified severity categories.
One two-hour exposure starting one hour after hemorrhage; outcomes at 24 and 72 hours.
A two-hour chamber exposure began one hour after SAH using premixed 2.9% H₂, 20% O₂ and balance nitrogen.
Premixed H₂/O₂/N₂ inhalation — not Brown's gas: the H₂:O₂ proportions were 2.9:20 rather than 2:1.
Total gas flow was 8 L/min for the first five minutes, then 6 L/min. Therefore H₂ flow was 232 mL/min initially and 174 mL/min during maintenance; O₂ flow was 1,600 mL/min initially and 1,200 mL/min during maintenance. These are direct calculations from the source's reported composition and total flows.
232 mL/min for the first 5 minutes; 174 mL/min thereafter.
20% O₂: 1,600 mL/min for the first 5 minutes; 1,200 mL/min thereafter.
Sham-operated rats and SAH rats breathing the control condition without the H₂ mixture.
Outcomes and reported result
Mortality, hemorrhage grade, neurological score, body weight, brain edema, blood-brain-barrier permeability, apoptosis and lipid/protein/DNA oxidative-damage markers.
At 24 hours H₂ reduced edema, barrier leakage, apoptosis and oxidative markers and improved neurological score. Mortality was not significantly different (15.3% vs 9.8%); body weight was unchanged; neurological improvement and edema reduction were absent at 72 hours; Evans-blue reduction at 24 hours was absent in cerebellum and brainstem. The authors described the benefit as transient.
The complete free PMC article was checked for allocation, exclusions, exact gas composition, total flows, calculated H₂/O₂ flows, timing, 24- and 72-hour positive/null outcomes, limitations, funding and conflicts.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Single short exposure in a rat model, severity-based exclusions, many surrogate endpoints, no durable benefit at 72 hours and no human participants. NIH grant support was reported; authors disclosed no potential conflicts.
Experimental subarachnoid hemorrhage in adult male rats; it does not establish an inhalation treatment for patients.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 22336722 · DOI: 10.1097/CCM.0b013e31823da96d
Free full author manuscript in PubMed Central.
Complete PMC author manuscript and PubMed metadata; full-text extraction checked 9 August 2026.
10 August 2026
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