Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice

Abstract

Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral white matter demyelination. The male C57 BL/6 mice with severe CO poisoning were treated by HBO. And HBO therapy shortened the escape latency and improved the body mass after CO poisoning. HBO therapy also significantly suppressed protein and mRNA levels of Notch1 and Hes5 after CO poisoning. Our findings suggested that HBO could suppress the activation of Notch signaling pathway after CO poisoning, which is the mechanism underlying the neuroprotection of HBO on demyelination after severe CO poisoning.

Keywords: Hes5; Notch signaling pathway; carbon monoxide poisoning; carboxyhemoglobin; demyelination; hyperbaric oxygen; oligodendrocyte; oligodendrocyte precursor cell; remyelination; white matter.

Figure 1

COHb content in CO poisoning models. Note: Data are expressed as mean ± SD (n = 3), *P < 0.05 (Kruskal-Wallis H test). CO: Carbon monoxide; COHb: carboxyhemoglobin.

Figure 2

Effect of HBO on the spatial learning and memory ability changes after CO poisoning. Note: (A) The swimming path during Morris water maze for each group. (B) The escape latency in CO group was significantly longer compared with that in sham group, and it was significantly shorter in CO+HBO group compared with that in CO group. Data are expressed as mean ± SD (n = 5), *P < 0.05 (one-way analysis of variance followed by Student-Newman-Keuls test). CO: Carbon monoxide; HBO: hyperbaric oxygen.

Figure 3

Effect of HBO on the change of body weight after CO poisoning. Note: Data are expressed as mean ± SD (n = 5), *P < 0.05 (one-way analysis of variance followed by Student-Newman-Keuls test). CO: carbon monoxide; HBO: hyperbaric oxygen.

Figure 4

Effect of HBO on the Notch1 and Hes5 protein expression in brain tissue after CO poisoning. Note: Data are expressed as mean ± SD (n = 5), *P < 0.05 (one-way analysis of variance followed by Student-Newman-Keuls test). CO: Carbon monoxide; HBO: hyperbaric oxygen.

Figure 5

Effect of HBO on the Notch1 and Hes5 mRNA expression in brain tissue after CO poisoning. Note: Data are expressed as mean ± SD (n = 5), *P < 0.05 (Mann-Whitney U test). CO: Carbon monoxide; HBO: hyperbaric oxygen.