Department of Basic Sciences, School of Veterinary Nursing and Technology, Faculty of Veterinary Sciences, Nippon Veterinary and Life Science University, Tokyo, Japan.
Center for Molecular Hydrogen Medicine, Keio University, Tokyo, Japan.
PLoS One. 2022 Dec 27;17(12):e0279410. doi: 10.1371/journal.pone.0279410. eCollection 2022.
Intraperitoneal administration of hydrogen (H2)-containing saline inhibited neuronal cell death in ischemic stroke in a number of animal models, but it is unknown whether H2 is absorbed from the abdominal cavity into the blood and reaches the brain. In this study, we investigated whether intraperitoneal administration of saline containing H2 inhibits neuronal cell death caused by cerebral ischemia and measured the concentration of H2 in the carotid artery and inferior vena cava (IVC). Gerbils were subjected to transient unilateral cerebral ischemia twice, and saline or H2-rich saline was administered intraperitoneally three or seven times every 12 hours. We evaluated the number of apoptotic cells in the hippocampus and cerebral cortex on day 3 and the number of viable neurons in the hippocampus and cerebral cortex on day 7. In addition, a single dose of saline or H2-rich saline was administered intraperitoneally, and blood H2 levels in the carotid artery and IVC were measured. On day 3 of ischemia/reperfusion, the number of neurons undergoing apoptosis in the cortex was significantly lower in the H2-rich saline group than in the saline group, and on day 7, the number of viable neurons in the hippocampus and cerebral cortex was significantly higher in the H2-rich saline group. Intraperitoneal administration of H2-rich saline resulted in large increases in H2 concentration in the IVC ranging from 0.00183 mg/L (0.114%) to 0.00725 mg/L (0.453%). In contrast, carotid H2 concentrations remained in the range of 0.00008 mg/L (0.0049%) to 0.00023 (0.0146%). On average, H2 concentrations in carotid artery were 0.04 times lower than in IVC. These results indicate that intraperitoneal administration of H2-rich saline significantly suppresses neuronal cell death after cerebral ischemia, even though H2 hardly reaches the brain.
腹腔内给予含氢气（H2）的生理盐水可抑制多种动物模型缺血性卒中的神经元细胞死亡，但尚不清楚 H2 是否从腹腔吸收进入血液并到达大脑。在这项研究中，我们研究了腹腔内给予含 H2 的生理盐水是否可抑制脑缺血引起的神经元细胞死亡，并测量颈总动脉和下腔静脉（IVC）中的 H2 浓度。沙土鼠接受两次短暂单侧脑缺血，每隔 12 小时腹腔内给予生理盐水或富含 H2 的生理盐水 3 或 7 次。我们在第 3 天评估海马和大脑皮层中的凋亡细胞数量，在第 7 天评估海马和大脑皮层中的存活神经元数量。此外，单次给予生理盐水或富含 H2 的生理盐水，测量颈总动脉和 IVC 中的血液 H2 浓度。在缺血/再灌注的第 3 天，富含 H2 的生理盐水组大脑皮层中的凋亡神经元数量明显低于生理盐水组，在第 7 天，富含 H2 的生理盐水组海马和大脑皮层中的存活神经元数量明显更高。腹腔内给予富含 H2 的生理盐水导致 IVC 中的 H2 浓度从 0.00183mg/L（0.114%）大幅增加到 0.00725mg/L（0.453%）。相比之下，颈总动脉中的 H2 浓度仍保持在 0.00008mg/L（0.0049%）至 0.00023mg/L（0.0146%）。平均而言，颈总动脉中的 H2 浓度比 IVC 低 0.04 倍。这些结果表明，即使 H2 很难到达大脑，腹腔内给予富含 H2 的生理盐水也可显著抑制脑缺血后的神经元细胞死亡。
