Table 3.

Molecular Hydrogen Use in Experimental TBI

Inhaled gas study	Form	Timing after injury (duration)	TBI type (severity)	Subject	Outcomes assessed	Findings
Hydrogen gas63	Hydrogen rich water (0.63-0.82 mmol/L) IP	5 min (IP injection daily for 1 day, 2 days, 3 days, 14 days duration)	Controlled cortical impact (moderate)	Rats	Whole–brain (inflammatory cytokines), hippocampus (Iba-1, synapsin I)	Reduced TNF-α, IL-1β, HGMB1, Iba-1, inflammatory metabolites on MRS; increased IL-10, synapsin 1, improved cognitive function
Hydrogen gas67	Inhaled 2% H2	30 min (4.5 h)	Controlled cortical impact (moderate)	Rats	Pericontusional microRNA-21	Reduced microRNA-21, cerebral edema, contusion volume, blood–brain barrier permeability, oxidative stress; improved cognitive function
Hydrogen gas64	Inhaled 2% H2	Immediately post-injury (5 h)	Controlled cortical impact (moderate)	Rats	Cerebral cortex Injury	Reduced blood–brain barrier permeability, cerebral edema, lesion volume, improved cognitive function, reduced markers of oxidative stress

TBI, traumatic brain injury; IP, intraperitoneal; TNF, tumor necrosis factor; HGMBI1, High mobility group box 1; MRS, magnetic resonance spectroscopy.