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

Abstract

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.

Effects of Prenatal Electronic Cigarette Exposure On Foetal Development: a Review of the Literature

“…An altogether decreased neuronal metabolism was noted. This became evident by a reduction in glucose uptake, expression of glucose transporters, adenosine triphosphate content, as well as a lower mitochondrial membrane potential 22 . E-cigarette exposure also led to reduced cell viability and increased DNA damage 22 .…”

“…This became evident by a reduction in glucose uptake, expression of glucose transporters, adenosine triphosphate content, as well as a lower mitochondrial membrane potential 22 . E-cigarette exposure also led to reduced cell viability and increased DNA damage 22 . In addition, the researchers found increased sensitivity of the mice to postnatal hypoxic-ischaemic brain injury caused by prenatal exposure to +Nic e-cigarettes, which is also seen in neonates with inadequate oxygen supply.…”

“…Letztere umfassen, neben Studien zu pulmonalen Folgen (n = 4 Studien), Studien zu kardiovaskulären Folgen (n = 2 Studien), gesichtsmorphologischen Folgen (n = 1 Studie) und renalen, die Niere betreffenden Folgen (n = 1 Studie). [22]. Die E-Zigaretten-Exposition führte zudem zu einer verminderten Zellvitalität und einer erhöhten DNA-Schädigung [22].…”

“…[22]. Die E-Zigaretten-Exposition führte zudem zu einer verminderten Zellvitalität und einer erhöhten DNA-Schädigung [22]. Weiter zeigten die Forscher eine durch pränatale E-Zigaretten-Exposition +Nik bedingte, erhöhte Sensibilität der Mäuse für postnatale hypoxisch-ischämische Hirnverletzungen, die auch bei Neugeborenen durch eine unzureichende Sauerstoffversorgung entsteht.…”

Cerebrovascular and Neurological Dysfunction under the Threat of COVID-19: Is There a Comorbid Role for Smoking and Vaping?

“…Moreover, it may facilitate the onset of stroke and worsen the condition of post-ischemic brain injury [75]. Another recent study also reported that e-cigarette vaping may decrease neuronal glucose utilization, which could result in increased risk for ischemic brain injury and stroke [135]. Recently, McAlinden et al suggested that, nicotine-based e-cigarettes or vaping may contribute to the upregulation of ACE2 which may also play an important role in progression and outcome of COVID-19 [136].…”