No 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.

The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity is vital to maintain the homeostasis of the brain microenvironment by controlling the passage of substances and regulating the trafficking of immune cells between the blood and the brain. The BBB is primarily composed of highly specialized microvascular endothelial cells. These cells’ special features and physiological properties are acquired and maintained through the concerted effort of hemodynamic and cellular cues from the surrounding environment. This complex multicellular system, comprising endothelial cells, astrocytes, pericytes, and neurons, is known as the neurovascular unit (NVU). The BBB strictly controls the transport of nutrients and metabolites into brain parenchyma through a tightly regulated transport system while limiting the access of potentially harmful substances via efflux transcytosis and metabolic mechanisms. Not surprisingly, a disruption of the BBB has been associated with the onset and/or progression of major neurological disorders. Although the association between disease and BBB disruption is clear, its nature is not always evident, specifically with regard to whether an impaired BBB function results from the pathological condition or whether the BBB damage is the primary pathogenic factor prodromal to the onset of the disease. In either case, repairing the barrier could be a viable option for treating and/or reducing the effects of CNS disorders. In this review, we describe the fundamental structure and function of the BBB in both healthy and altered/diseased conditions. Additionally, we provide an overview of the potential therapeutic targets that could be leveraged to restore the integrity of the BBB concomitant to the treatment of these brain disorders.