Abstract
Cognitive impairment is the most common neurologic sequelae after carbon monoxide (CO) poisoning, and the previous investigations have demonstrated that N-Butylphthalide (NBP) could exert a broad spectrum of neuroprotective properties. The current study aimed to investigate the effect of NBP on cognitive dysfunction in rats after acute severe CO poisoning. Rats were randomly divided into a normal control group, a CO poisoning group and a CO+NBP group. The animal model of CO poisoning was established by exposure to CO in a chamber, and then all rats received hyperbaric oxygen therapy once daily, while rats in CO+NBP group were administered orally NBP (6 mg/ 100g) by gavage twice a day additionally. The results indicated that CO poisoning could induce cognitive impairment. The ultrastructure of hippocampus was seriously damaged under transmission electron microscopy, and the expressions of calpain 1 and CaMK II proteins were significantly elevated after CO exposure according to the analysis of immunofluorescence staining and western blot. NBP treatment could evidently improve cognitive function, and maintain ultrastructure integrity of hippocampus. The expression levels of both calpain 1 and CaMK II proteins in CO+NBP group were considerably lower than that of CO poisoning group (P < 0.05). Taken together, this study highlights the molecular mechanism of cognitive dysfunction in rats after CO exposure via the upregulation of both calpain 1 and CaMK II proteins. The administration of NBP could balance the expressions of calpain 1 and CaMK II proteins and improve cognitive function through maintaining ultrastructural integrity of hippocampus, and thus may play a neuroprotective role in brain tissue in rats with CO poisoning.
Highlights
From a public health perspective, unintentional carbon monoxide (CO) poisoning is a leading factor of accidental poisoning in the United States, and may be the cause of more than 50% fatal poisonings in many industrial countries (Omaye, 2002; Geraldo et al, 2014)
The difference between the two groups was extremely significant at a late stage of CO poisoning (>1 weeks, P < 0.05), yet no significant difference was found at an early stage of poisoning ( 0.05)
These results suggested that acute CO poisoning could decrease the ability of spatial learning and memory in rats, which may be closely related to the duration of CO exposure
Summary
From a public health perspective, unintentional carbon monoxide (CO) poisoning is a leading factor of accidental poisoning in the United States, and may be the cause of more than 50% fatal poisonings in many industrial countries (Omaye, 2002; Geraldo et al, 2014). Few investigations evaluate the relationship between the cognitive impairment and hippocampus damage after exposure to CO (Chen et al, 2013). It has been demonstrated that NBP could efficiently improve cognitive deficits induced by chronic intermittent hypoxia (IH)-hypercapnia exposure (Min et al, 2014), protect cells against ischemic damage via multiple mechanisms including mitochondria associated caspase-dependent and -independent apoptotic pathways both in vitro and in vivo (Li et al, 2010; Wang et al, 2014), maintain mitochondrial function and balance the expressions of anti-apoptosis genes and pro-apoptosis genes. We aimed to investigate the underlying mechanisms of cognitive dysfunction in rat models after exposure to CO, and evaluate the feasibility of NBP treatment on the structural and functional impairment of hippocampus induced by acute severe CO poisoning
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