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Protective effects of hydrogen gas against spinal cord ischemia–reperfusion injury

      Abstract

      Objective

      This experimental study aimed to assess the efficacy of hydrogen gas inhalation against spinal cord ischemia–reperfusion injury and reveal its mechanism by measuring glutamate concentration in the ventral horn using an in vivo microdialysis method.

      Methods

      Male Sprague-Dawley rats were divided into the following 6 groups: sham, only spinal ischemia, 3% hydrogen gas (spinal ischemia + 3% hydrogen gas), 2% hydrogen gas (spinal ischemia + 2% hydrogen gas), 1% hydrogen gas (spinal ischemia + 1% hydrogen gas), and hydrogen gas dihydrokainate (spinal ischemia + dihydrokainate [selective inhibitor of glutamate transporter-1] + 3% hydrogen gas). Hydrogen gas inhalation was initiated 10 minutes before the ischemia. For the hydrogen gas dihydrokainate group, glutamate transporter-1 inhibitor was administered 20 minutes before the ischemia. Immunofluorescence was performed to assess the expression of glutamate transporter-1 in the ventral horn.

      Results

      The increase in extracellular glutamate induced by spinal ischemia was significantly suppressed by 3% hydrogen gas inhalation (P < .05). This effect was produced in increasing order: 1%, 2%, and 3%. Conversely, the preadministration of glutamate transporter-1 inhibitor diminished the suppression of spinal ischemia-induced glutamate increase observed during the inhalation of 3% hydrogen gas. Immunofluorescence indicated the expression of glutamate transporter-1 in the spinal ischemia group was significantly decreased compared with the sham group, which was attenuated by 3% hydrogen gas inhalation (P < .05).

      Conclusions

      Our study demonstrated hydrogen gas inhalation exhibits a protective and concentration-dependent effect against spinal ischemic injury, and glutamate transporter-1 has an important role in the protective effects against spinal cord injury.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      ANOVA (analysis of variance), DHK (dihydrokainate), d-ROM (diacron-reactive oxygen metabolite), H2 (hydrogen), MDI (motor deficit index), MEP (motor-evoked potential), ROS (reactive oxygen species), SCI (spinal cord ischemia), TAA (thoracoabdominal aortic), TRP (transient receptor potential)
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