Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic–ischemic brain injury

• Published in: Journal of neurochemistry 2020-04, Vol.153 (1), p.63-79
• Main Authors: Sifat, Ali E., Nozohouri, Saeideh, Villalba, Heidi, Al Shoyaib, Abdullah, Vaidya, Bhuvaneshwar, Karamyan, Vardan T., Abbruscato, Thomas
• Format: Article
• Language: English
• Subjects: Brain; brain glucose utilization; Brain injury; Cell viability; Cognitive ability; Deprivation; Edema; Electronic cigarettes; Exposure; Fetuses; Glucose; Glucose metabolism; Head injuries; Hypoxia; Immunofluorescence; Injury analysis; Injury prevention; Ischemia; Juveniles; maternal e‐cigarette; motor and cognitive functions; Motor skill learning; neonatal hypoxic–ischemic brain injury; Neurons; Nicotine; Object recognition; Offspring; Pattern recognition; Prenatal experience; Sensitivity enhancement; Tobacco; Traumatic brain injury; Triphenyltetrazolium chloride; Utilization; Vapors; Western blotting
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.14947

It has been shown that prenatal nicotine and tobacco smoke exposure can cause different neurobehavioral disorders in the offspring. We hypothesize that prenatal exposure to nicotine‐containing electronic cigarette (e‐Cig) vapor can predispose newborn to enhanced sensitivity to hypoxic–ischemic (HI) brain injury and impaired motor and cognitive functions. In this study, pregnant CD1 mice were exposed to e‐Cig vapor (2.4% nicotine). Primary cortical neurons isolated from e‐Cig exposed fetus were exposed to oxygen–glucose deprivation followed by reoxygenation (OGD/R) to mimic HI brain injury. Cell viability and glucose utilization were analyzed in these neurons. HI brain injury was induced in 8–9‐day‐old pups. Short‐term brain injury was evaluated by triphenyltetrazolium chloride staining. Long‐term motor and cognitive functions were evaluated by open field, novel object recognition, Morris water maze, and foot fault tests. Western blotting and immunofluorescence were done to characterize glucose transporters in offspring brain. We found that e‐Cig exposed neurons demonstrated decreased cell viability and glucose utilization in OGD/R. Prenatally e‐Cig exposed pups also had increased brain injury and edema 24 hr after HI brain injury. Further, in utero e‐Cig exposed offspring with HI brain injury displayed impaired memory, learning, and motor coordination at adolescence. Additionally, the expression of glucose transporters decreased in e‐Cig exposed offspring brain after HI brain injury. These results indicate that reduced glucose utilization can contribute to prenatal e‐Cig exposure induced worsened HI brain injury in offspring. This study is instrumental in elucidating the possible deleterious effects of e‐Cig use in the general population. This study intended to investigate the effects of maternal electronic cigarette (e‐Cig) exposure on offspring hypoxic‐ischemic brain injury. We found increased sensitivity to hypoxic‐ischemic brain injury along with decreased brain glucose utilization and the expression of brain glucose transporters, and impaired motor and cognitive function in e‐Cig exposed offspring after hypoxic‐ischemic brain injury. This study demonstrates one of the possible deleterious effects of e‐Cig use during pregnancy.