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| Action mechanism of hyperbaric oxygen on white matter damage in adult rats with hypoxic-ischemic encephalopathy |
| XUE Ruijun1 LI Wenping2 HUANG Weizhe3 PAN Shuyi1 GUO Dazhi1 |
1.Department of Hyperbaric Oxygen, the Six Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100048, China;
2.Department of Imagining, the Six Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100048, China;
3.Department of Hyperbaric Oxygen, Ninth People’s Hospital of Zhengzhou, Henan Province, Zhengzhou 450053, China
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Abstract Objective To investigate the action mechanism of hyperbaric oxygen (HBO) on white matter damage in adult rats with hypoxic-ischemic encephalopathy. Methods Forty-eight ten- week-old clean grade male SD rats aged 300-350 g were divided into four groups by completely randomized method: control group (no treatment), sham operation group (the skin was sutured directly after only bilateral carotid arteries were exposed), model group (two weeks after bilateral carotid arteries were ligation, rats were placed in a sealed chamber with 8%O2 and 92%N2 mixture for three hours), HBO group (HBO treatment was immediately given on the basis of model group), 12 rats in each group. The learning and memory function was evaluated by water maze before modeling and in the 4th week respectively. Fast Blue staining was used to observe the white matter myelin sheath damage in rat hippocampus. The expressions of ionized calcium binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) in the hippocampus were determined by immunofluorescence method. The expressions of myelin basic protein (MBP), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in hippocampus were analyzed by Western blot. Results There were no significant differences in the average incubation period and the number of platform crossing between the sham operation group and the control group (P＞0.05). The average incubation period of the model group was longer than that of the control group, and the number of platform crossing was lower than that of the control group (P＜0.05). The average incubation period of the HBO group was shorter than that of model group, and the number of platform crossing was higher than that of the model group (P＜0.05). The sham operation group was compared with the control group, the hippocampal staining degree of rats was basically the same, and there was no significant difference in myelin sheath. Compared with the control group, the hippocampal staining of rats was weakened, the myelin sheath was reduced, and vacuoles were appeared in some areas in the model group. Compared with the model group, hippocampal staining degree of rats was improved, myelin sheath was increased and regional vacuoles were decreased significantly in the HBO group. There was no significant difference in the number of GFAP-positive activated astrocytes and Iba-1 positive activated microglia in the hippocampus between the sham operation group and the control group (P＞0.05). The number of GFAP-positive activated astrocytes and Iba-1 positive activated microglia in the hippocampus of the model group was higher than that of the control group (P＜0.05). The number of GFAP-positive activated astrocytes and Iba-1 positive activated microglia in hippocampus of the HBO group was lower than that of the model group (P＜0.05). There were no significant differences in the expressions of MBP, IL-1β, IL-6, and TNF-α between the sham operation group and the control group (P＞0.05). The expression of MBP protein in the brain of the model group was lower than that of the control group, and the expressions of IL-1β, IL-6, and TNF-α were higher than those of the control group (P＜0.05). The expression of MBP protein in the HBO group was higher than that in the model group, but the expression levels of IL-1β, IL-6, and TNF-α in the HBO group were lower than that in the model group (P＜0.05). Conclusion HBO may reduce the activation of microglias and astrocytes in the hippocampus, inhibit the release of inflammatory factors, relieve myelin sheath damage, and promote myelin sheath regeneration, thereby improving the cognitive impairment of adult rats with hypoxic-ischemic encephalopathy.
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