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Page 6 of 10 Balistreri. Vessel Plus 2018;2:25 I http://dx.doi.org/10.20517/2574-1209.2018.35

ischemia-reperfusion injury and in pre-clinical models of PH. Furthermore, the traditional high-nitrate diet
[34]
is associated with beneficial outcomes in hypertension, obesity and cardiovascular diseases .

POTENTIAL MEASURES OF INTERVENTIONS FOR IMPROVING FOETAL PROGRAMMING AND
THE DEVELOPMENT OF TARGET BODY SYSTEMS?
It is well established that adverse events, taking place during the early periods of human development,
mediate deleterious effects on health and disease molecular patterns of new progeny over his life course. This
[8]
concept of health and disease origin is also leading to the study of the existence of relationships between
the improving of foetal programming and the change of one determined lifestyle behaviour. For example,
including the quantity of food intake and its quality, oral supplementation of prebiotics and/or probiotics,
[35]
drug molecules, feeding preferences or willingness to engage in physical activities, etc. . Beneficial results
from use of their administration could lead to propose them as very programs of health, like to those
recently projected by our institutions and organizations for improving “health” in our growing aged society
having a high susceptibility for age-related diseases, such as cardiovascular diseases, pulmonary diseases,
type 2 diabetes, cancer and neurodegenerative diseases. Certainly, their results could also prove unsuccessful
because of the free will that characterizes the human nature in assuming choices on the behaviours to
adopt. This limits their application, and it makes more difficult the understanding that the behaviours
of everyone may also be the result of genetic and neurologic determinants mixed with the environment,
during the process of neurodevelopment. Another limitation might be the choice of tool for measuring
the consequent beneficial or lack of beneficial effects. One tool or parameter might be represented by fetal
growth. Poor fetal growth is significantly associated with the onset of many diseases mentioned above.
Specifically, IUGR represents a typical model, and is caused by, but not restricted to, placental insufficiency,
maternal malnutrition and smoking, congenital infections and anomalies, drugs, obesity and chromosomal
abnormalities. In low and middle-income countries, IUGR achieves the proportion of 27%.

Some interventions are described in the subsequent paragraphs, stressing their advantageous effects.

Physical activity
Physical activity has been demonstrated to have many beneficial effects on diverse pathological conditions.
In addition, it improves not only the physical health, but also the mental health. As stressed in my recent
[35]
review, it represents a very useful intervention in old people . In addition, exercise increases brain
connectivity between the frontal, posterior, and temporal cortices, influences hippocampal volume and
[36]
serum levels of brain-derived neurotrophic factor (BDNF) , a mediator of neurogenesis in the dentate gyrus
[36]
of the hippocampus . From a neurobiological standpoint, exercise modulates the production and release of
[36]
cortisol, endocannabinoids, BDNF, dopamine and serotonin . Specifically, the transient stress’s response
related to physical exercise evocates inhibitory effects from the secreted cortisol upon the hypothalamus
and pituitary through medial prefrontal cortex receptors and reduces stress-induced over-excitability of the
amygdala [35,36] . Moreover, aerobic exercise decreases the quantity of competitive amino acids during muscle
uptake, and enhances tryptophan’s chances of crossing the blood-brain barrier, and consequently it mediates
the augmentation of serotonin, an important neurotransmitter for emotional processing, satiety and memory
functions [35,36] . These might represent some of the potential targets of future research, particularly the study
of the neurobiological effects of exercise in susceptible populations such as those born with IUGR [35,36] .
Consequently, further research might benefit from recruiting IUGR individuals as appropriate subjects for
evaluating interventions on physical activity in well designed, large-scale longitudinal studies, for detecting
potential beneficial effects. Furthermore, basic neurobiological examinations on the effects of exercise in this
group might also be performed. They could facilitate the identification of the mechanisms that better adapt
to such interventions [35,36] .