The interaction of zinc and the blood-brain barrier under physiological and ischemic conditions

Abstract

Zinc is the second most abundant metal in human and serves as an essential trace element in the body. During the past decades, zinc has been found to play important roles in central nervous system, such as the development of neurons and synaptic activities. An imbalance of zinc is associated with brain diseases. The blood-brain barrier (BBB) maintains the homeostasis of the microenvironment, regulating the balance of zinc in the brain. A compromised BBB is the main cause of severe complications in cerebral ischemic patients, such as hemorrhage transformation, inflammation and edema. Recent studies reported that zinc in the brain may be a potential target for integrative protection against ischemic brain injury. Although zinc has long been regarded as important transmitters in central nervous system, the critical role of zinc dyshomeostasis in damage to the BBB has not been fully recognized. In this review, we summarize the role of the BBB in regulating homeostasis of zinc in physiological conditions and the effects of changes in zinc levels on the permeability of the BBB in cerebral ischemia. The integrity of BBB maintains the homeostasis of zinc in pathological conditions, while the balance of zinc in the brain and the circulation maintains the normal function of the BBB. Interrupting the zinc/BBB system will disturb the microenvironment in the brain, leading to pathological diseases. In stroke patients, zinc may serve as a potential target for protecting the BBB and reducing hemorrhage transformation, inflammation and edema.

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“…Another nutrient, zinc, is crucial for memory formation and learning [ 68 ]. Zinc is necessary in forming synapses and in mediating structural plasticity; this activity potentially allows zinc to modulate the function of the hippocampus in memory [ 69 ].…”

“…Animal studies have shown that psychological stress reduces serum zinc levels, implying that zinc deficiencies and gut inflammation are linked to stress [ 75 ]. Zinc is also essential in the general development and function of the central nervous system (CNS) [ 68 ]. Long-term administration of zinc sulfate in rats enhanced learning, spatial memory, and exploratory activity [ 10 ].…”

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

“…Close relationships also exist between the blood-brain barrier (BBB) and zinc. While the BBB is of great importance for maintaining zinc homeostasis in the brain, a proper balance between the zinc in the systemic circulation and in the brain is important for normal BBB function [ 60 ]. A disturbance of the zinc BBB system affects the microenvironment in the brain, which can lead to pathological damage.…”

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“…At the molecular level, Zn is responsible for neuronal metabolism and plasticity, as well as synaptic activity. Thus, imbalances in Zn levels (especially increased concentrations) and further Zn accumulation within the CNS leads to neuronal damage via excitotoxicity, oxidative stress, and impaired cellular energy generation [ 80 , 238 , 239 ]. Zn deficiency during pregnancy and its insufficient levels during child development are associated with a higher probability of mental retardation, apathy, lethargy, and impaired learning ability [ 240 , 241 ].…”