The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced with dopamine or dobutamine infusion

Inocencio, Ishmael M.; Tran, Nhi T.; Khor, Song J.; Wiersma, Manon; Nakamura, Shinji; Walker, David; Wong, Flora Yuen-Wait

doi:10.1016/j.expneurol.2021.113687

Cited by 4 publications

(14 citation statements)

References 51 publications

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“…Between the preterm and 7–10-day old term lambs, we did not identify any differences in the peak amplitude or latency of the positive ΔoxyHb response in this current cohort or our published data of newborn lambs. 24,25 Nevertheless, our current SR findings suggest the underlying vascular mechanisms are evidently different between the 7–10-day old term brain and preterm brain.…”

Section: Discussionmentioning

confidence: 53%

“…The fetal left median nerve was exposed at the cubital fossa of the forelimb and a small silicon cuff containing two multi-stranded copper wire electrodes approximately 1 cm apart was placed around the median nerve. 25 The fetal lamb was then intubated (size 4.0 endotracheal tube) and lung liquid passively drained for 2 mins. The lamb was then fully exteriorized from the uterus onto the maternal abdomen, with the umbilical cord still attached and functioning, for positive pressure ventilation with humidified air in volume-guaranteed mode at tidal volumes of $5 ml/ kg using a (Babylog8000þ, Draeger; Germany).…”

Section: Surgery and Lamb Instrumentationmentioning

confidence: 99%

“…The light emitters and detector optodes of a twochannel tissue oxygenation probe (NIRO-200, Hamamatsu Photonics, Japan) were placed bilaterally on the shaved scalp of the lamb, over the somatosensory cortex. 24,25 Measurement of changes in DoxyHb, DdeoxyHb and total haemoglobin (Dtotal Hb ¼ DoxyHbþ DdeoxyHb) (mM.cm) in both hemispheres were recorded continuously.…”

Section: Near Infrared Spectroscopy (Nirs)mentioning

confidence: 99%

“…These observations are consistent with our previous studies demonstrating that somatosensory stimulation evokes variable responses in 7-10day old term lambs 24 and mostly positive cerebral hemodynamic responses in preterm lambs. 25 Changes in blood pressure and cerebral DHb after somatosensory stimulation (Table 2) Mean arterial blood pressure. Combining the 7-10-day old term lambs with positive and negative responses, there is no difference in their mean peak DMABP compared to that in preterm lambs following 4.8 or 7.8 sec stimulations.…”

Section: Nirs Measurement Of Cerebral Haemodynamic Responses To Somat...mentioning

confidence: 99%

“…22 Indeed, preterm sheep have been used extensively to define the pathophysiology of the preterm cerebral circulation, 23 and we have previously used the NIRS technique in fetal, preterm and term lambs to study cerebral haemodynamic responses provoked by somatosensory stimulation. 16,24,25 In this study, we exploited the potential of monochromatic SR microangiography together with NIRS to study functional cerebral haemodynamics in preterm and 7-10-day old term lambs for the first time. We aimed to investigate the microvascular changes underlying the cerebral haemodynamic responses in the immature brain.…”

Section: Introductionmentioning

confidence: 99%

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Cerebral haemodynamic response to somatosensory stimulation in preterm lambs and 7–10-day old lambs born at term: Direct synchrotron microangiography assessment

Inocencio

Tran

Nakamura

et al. 2021

J Cereb Blood Flow Metab

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Neurovascular coupling has been well-defined in the adult brain, but variable and inconsistent responses have been observed in the neonatal brain. The mechanisms that underlie functional haemodynamic responses in the developing brain are unknown. Synchrotron radiation (SR) microangiography enables in vivo high-resolution imaging of the cerebral vasculature. We exploited SR microangiography to investigate the microvascular changes underlying the cerebral haemodynamic response in preterm (n = 7) and 7–10-day old term lambs (n = 4), following median nerve stimulation of 1.8, 4.8 and 7.8 sec durations. Increasing durations of somatosensory stimulation significantly increased the number of cortical microvessels of ≤200 µm diameter in 7–10-day old term lambs (p < 0.05) but not preterm lambs where, in contrast, stimulation increased the diameter of cerebral microvessels with a baseline diameter of ≤200 µm. Preterm lambs demonstrated positive functional responses with increased oxyhaemoglobin measured by near infrared spectroscopy, while 7–10-day old term lambs demonstrated both positive and negative responses. Our findings suggest the vascular mechanisms underlying the functional haemodynamic response differ between the preterm and 7–10-day old term brain. The preterm brain depends on vasodilatation of microvessels without recruitment of additional vessels, suggesting a limited capacity to mount higher cerebral haemodynamic responses when faced with prolonged or stronger neural stimulation.

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Section: Discussionmentioning

confidence: 53%

Section: Surgery and Lamb Instrumentationmentioning

confidence: 99%

Section: Near Infrared Spectroscopy (Nirs)mentioning

confidence: 99%

Section: Nirs Measurement Of Cerebral Haemodynamic Responses To Somat...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs and 7–10-day old lambs born at term: Direct synchrotron microangiography assessment

Inocencio

Tran

Nakamura

et al. 2021

J Cereb Blood Flow Metab

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Near-infrared spectroscopy monitoring of neonatal cerebrovascular reactivity: where are we now?

et al. 2023

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

Tran,

Hale,

Maung

et al. 2024

J Neuroinflammation

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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.

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The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced with dopamine or dobutamine infusion

Cited by 4 publications

References 51 publications

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs and 7–10-day old lambs born at term: Direct synchrotron microangiography assessment

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs and 7–10-day old lambs born at term: Direct synchrotron microangiography assessment

Near-infrared spectroscopy monitoring of neonatal cerebrovascular reactivity: where are we now?

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

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