The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced following intrauterine inflammation and dopamine infusion

Inocencio, Ishmael M.; Tran, Nhi T.; Wiersmac, Manon; Stoecker, Katja; Nakamura, Shinji; Moss, Timothy; Walker, David; Wong, Flora Yuen-Wait

doi:10.1016/j.expneurol.2022.114049

Cited by 3 publications

(6 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disturbances of the NVU physiology and morphology have been identified as one of the leading causes of neurodevelopmental disorders [ 23 ]. We have previously demonstrated in preterm lambs that exposure to intrauterine inflammation results in a negative cerebral functional haemodynamic response following somatosensory stimulation [ 8 ]. This negative haemodynamic response suggested impaired neurovascular coupling, possibly reflecting cellular changes at the level of the NVU.…”

Section: Discussionmentioning

confidence: 99%

“…This study utilized post-mortem preterm lamb brain tissue collected after in vivo physiological studies as previously published [ 8 ]. The use of animals was approved by Monash Medical Centre Animal Ethics Committee (MMCA-2016/17 and 2016/23) and was conducted in accordance with the Australian Code of Practice for the care and use of Animals for Scientific Purposes established by the National Health and Medical Research Council of Australia.…”

Section: Methodsmentioning

confidence: 99%

“…But they can have an even greater and disproportionate increase in cerebral oxygen consumption and oxygen extraction [ 7 ], indicating a baseline mismatch between the cerebral oxygen delivery and oxygen consumption. We have reported that preterm lambs exposed to intrauterine inflammation, induced by intra-amniotic injection of lipopolysaccharide (LPS), are more likely to show a negative cerebral functional haemodynamic response (i.e., localised decrease in oxyhaeomoglobin) suggesting that neuronal activity, which increases the demand for oxygen, is likely to create localized oxygen deficits [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Given the adverse long-term consequence of chorioamnionitis, insights into the neurovascular effects of intrauterine inflammation in the preterm brain, particularly on the NVU, will be important for understanding the events that lead to brain injury, dysfunction, and repair, as well as identification of therapeutic targets. In addition, we have previously reported that infusion of the inotrope dopamine, often required to treat hypotensive preterm infants following infection/inflammation, increases the baseline cerebral oxygenation but also further increases the incidence of negative functional haemodynamic responses in preterm lambs exposed to intrauterine inflammation [ 8 , 14 ]. To fully understand the implications of these effects on neurovascular coupling, histopathological analysis of the NVU would provide mechanistic insights at the cellular and molecular levels.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs

Tran,

Hale,

Maung

et al. 2024

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

Background Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses. Methods At 119–120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3–4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit. Results LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte “end feet” vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS. Conclusion LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs

Tran,

Hale,

Maung

et al. 2024

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

show abstract

“…5 Studies in neonatal rats and fetal sheep have shown that perinatal systemic inflammation is associated with neuroinflammation, white matter damage and neuronal loss, as well as hypotension with generalised vasodilation and altered neurovascular coupling. [6][7][8][9] However, the majority of these studies used a cell wall component of gram-negative bacteria (lipopolysaccharide; LPS) to induce inflammation. Surprisingly, there have been few studies of gram-positive bacteria such as group B streptococcus (GBS), which are a major contributor in many countries to adverse maternal and neonatal outcomes.…”

Section: Introductionmentioning

confidence: 99%

The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep

Dhillon,

Lear,

Davidson

et al. 2023

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function.

show abstract

Effect of Combining Intrauterine Cerebral Blood Flow Changes with Electrical Activity on Prognostic Evaluation of Brain Injury

Yao,

Zhang,

Qiu

2024

World Neurosurgery

View full text Add to dashboard Cite

The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced following intrauterine inflammation and dopamine infusion

Cited by 3 publications

References 49 publications

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs

The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep

Effect of Combining Intrauterine Cerebral Blood Flow Changes with Electrical Activity on Prognostic Evaluation of Brain Injury

Contact Info

Product

Resources

About