Neuroprotective effect of targeted regulatory Nrf2 gene on rats with acute brain injury induced by carbon monoxide poisoning

Abstract

Oxidative stress has been considered as an important cause of neurocyte damage induced by carbon monoxide (CO) poisoning; however, the precise mechanisms are not fully understood. The study aimed to elucidate the molecular mechanism and the neuroprotective effect of targeted regulatory nuclear factor erythroid2‐related factor 2 (Nrf2) gene on acute brain injury in CO poisoning rats. An acute CO poisoning rat model was established by CO inhalation in hyperbaric oxygen chamber and followed by the administration of Nrf2 gene‐loaded lentivirus. Mitochondrial membrane potential (ΔΨM), the levels of Nrf2, glutamate‐cysteine ligase catalytic subunit (GCLC), catalase (CAT) and glutathione peroxidase (GSH‐Px), and cell apoptosis were determined in brain tissue in rats. We found that CO poisoning could decrease ΔΨm of cells, slightly increase the expressions of Nrf2 and GCLC at mRNA and protein levels, reduce CAT and GSH‐Px, and thus initiate apoptosis process. The Nrf2 gene treatment could obviously enhance the expressions of Nrf2 at mRNA and protein levels, and increase the concentrations of CAT and GSH‐Px, maintain the ΔΨm of cells in brain tissue, significantly inhibit cell apoptosis as compared with the CO poisoning group (p < .05). These findings suggest that CO poisoning could induce oxidative stress and impair mitochondrial function of cells in brain tissue. The administration of Nrf2 gene could notably strengthen the antioxidant capacity of cells through regulating the downstream genes of Nrf2/antioxidant responsive element signal pathway, and positively protect cells against brain injury induced by acute severe CO poisoning.

Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation of Pueraria montana var. lobata and Schisandra sphenanthera

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Sodium butyrate exerts a neuroprotective effect in rats with acute carbon monoxide poisoning by activating autophagy through the mTOR signaling pathway

“…After carbon monoxide poisoning, the formation of COHb and the direct toxicity of CO lead to tissue hypoxia. Tissue hypoxia-induced oxidative stress and the neuroinflammatory response persists a long time after CO exposure, which induces apoptosis and necrosis of brain cells, ultimately leading to a wide range of neuropathological and physiological alterations 24 , 25 . In this study, we observed and analyzed the data on days one, seven, and 14 after CO poisoning.…”

Loganin attenuates neuroinflammation after ischemic stroke and fracture by regulating α7nAChR‐mediated microglial polarization

“…RNA extraction and RT‐qPCR detection were carried out as described previously 30 . Brain tissues of the mouse ipsilateral hemisphere were taken for RT‐qPCR analysis 3 days after operation.…”

“…RNA extraction and RT-qPCR detection were carried out as described previously. 30 Brain tissues of the mouse ipsilateral hemisphere were taken for RT-qPCR analysis 3 days after operation. TRIzol reagent (Invitrogen) was used to extract total RNA from cells and tissues in accordance with the manufacturer's protocol; 1 μg of extract RNA was reverse transcribed into Single-strand cDNA by using a First-strand cDNA Synthesis Kit (Takara).…”