New molecular markers to differentiate carbon dioxide intoxication from asphyxia due to oxygen deficiency

The lack of specific autopsy findings for carbon dioxide (CO₂) intoxication hinders the determination of cause of death based on autopsy findings alone. In addition, when death occurs in a space is filled with CO₂ or other gases, the cause of death must be distinguished between intoxication and asphyxia due to oxygen deficiency, which also has no specific autopsy findings. In this study, we aimed to identify diagnostic markers of mRNA expression in the brainstem that indicate cause of death in cases of suspected CO₂ intoxication.

Mouse models of CO₂ intoxication (composition of ambient gases at 70% CO₂, 20% O₂, and 10% N₂) and asphyxia due to oxygen deficiency (5% O₂, 95% N₂) were used to identify mRNA markers specific to intoxication or asphyxia.

Using RNA-Sequence analysis, we identified 7 candidate genes for qRT-PCR analysis: Acid-sensing ion channel 4 (Asic4), Early growth response protein 1 (Egr1), Neurogranin (Nrgn), Opioid receptor delta 1 (Oprd1), Semaphorin 3f (Sema3f), Transthyretin (Ttr), and Tryptophan hydroxylase 2 (Tph2). We observed a significant increase of Nrgn mRNA expression in the brainstem of CO₂ intoxication and a significant increase of Ttr mRNA expression in the brainstem of asphyxia due to oxygen deficiency.

Assays for the expression of Nrgn and Ttr in the human brainstem may assist in the diagnosis/differential diagnosis of CO₂ intoxication and asphyxia due to oxygen deficiency, respectively.