The balance between the pro-inflammatory effect of plasma noradrenaline and the anti-inflammatory effect of neuronal noradrenaline determines the peripheral effect of noradrenaline

Perfusion experiments on an isolated, canine lateral saphenous vein segment preparation have shown that noradrenaline causes potent, flow dependent effects, at a threshold concentration comparable to that of plasma noradrenaline, when it stimulates the segment by diffusion from its microcirculation (vasa vasorum). The effects caused are opposite to those neuronal noradrenaline causes in vivo and that, in the light of the principle that all information is transmitted in patterns that need contrast to be detected – star patterns need darkness, sound patterns, quietness – has generated the hypothesis that plasma noradrenaline provides the obligatory contrast tissues need to detect and respond to the regulatory information encrypted in the diffusion pattern of neuronal noradrenaline. Based on the implications of that hypothesis, the controlled variable of the peripheral noradrenergic system is believed to be the maintenance of a set point balance between the contrasting effects of plasma and neuronal noradrenaline on a tissue. The hypothalamic sympathetic centres are believed to monitor that balance through the level of afferent sympathetic traffic they receive from a tissue and to correct any deviation it detects in the balance by adjusting the level of efferent sympathetic input it projects to the tissue. The failure of the centres to maintain the correct balance, for reasons intrinsic or extrinsic to themselves, is believed to be responsible for degenerative and genetic disorders. When the failure causes the balance to be polarised in favour of the effect of plasma noradrenaline that is believed to cause inflammatory diseases like dilator cardiac failure, renal hypertension, varicose veins and aneurysms; when it causes it to be polarised in favour of the effect of neuronal noradrenaline that is believed to cause genetic diseases like hypertrophic cardiopathy, pulmonary hypertension and stenoses and when, in pregnancy, a factor causes the polarity to favour plasma noradrenaline in all the maternal tissues except the uterus and conceptus, where it favours neuronal noradrenaline, that is believed to cause preeclampsia.

The effect of positive psychological interventions on psychological and physical well-being during pregnancy

Prenatal well-being can have significant effects on the mother and developing foetus. Positive psychological interventions, including gratitude and mindfulness, consistently demonstrate benefits for well-being in diverse populations. No research has been conducted on gratitude during pregnancy; the few studies of prenatal mindfulness interventions have demonstrated well-being benefits. The current study examined the effects of gratitude and mindfulness interventions on prenatal maternal well-being, cortisol and birth outcomes. Five studies were conducted. Study 1 was a systematic review of mindfulness intervention effects on cortisol; this highlighted potential benefits of mindfulness but the need for rigorous protocols in future research. In Study 2 a gratitude and a mindfulness intervention were developed and evaluated; findings indicate usefulness of two 3 week interventions. Study 3 examined the effects of these interventions in a randomised controlled trial (RCT) of non-pregnant women, before examining a pregnant group. No significant intervention effects were found in this study, potentially due to insufficient power and poor protocol adherence. Changes in expected directions were observed for most outcomes and the potential utility of a combined gratitude and mindfulness intervention was noted. In Study 4 a gratitude during pregnancy (GDP) scale was developed and the reliability of an existing mindfulness measure (MAAS) was examined in a pregnant group. Both scales were found to be suitable and reliable measures in pregnancy. Study 5 incorporated the findings of the previous four studies to examine of the effect of a combined mindfulness and gratitude intervention with a group of pregnant women. Forty-six participants took part in a 5-week RCT that examined intervention effects on prenatal gratitude, mindfulness, happiness, satisfaction with life, social support, prenatal stress, depression and sleep. Findings indicated that the intervention improved sleep quality and that effects for prenatal distress were approaching significance. Issues of attrition and non-compliance to study protocols were problematic and are discussed. In summary, the current thesis highlights the need for robust measurement, and intervention and cortisol sampling protocols in future research, particularly with pregnant groups. Findings also demonstrate tentative benefits of a gratitude and mindfulness intervention during pregnancy.

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.