Cerebral Autoregulation Is Minimally Influenced by the Superior Cervical Ganglion in Two- Week-Old Lambs, and Absent in Preterm Lambs Immediately Following Delivery

Abstract

Cerebral vessels in the premature newborn brain are well supplied with adrenergic nerves, stemming from the superior cervical ganglia (SCG), but their role in regulation of blood flow remains uncertain. To test this function twelve premature or two-week-old lambs were instrumented with laser Doppler flow probes in the parietal cortices to measure changes in blood flow during changes in systemic blood pressure and electrical stimulation of the SCG. In lambs delivered prematurely at ∼129 days gestation cerebral perfusion and driving pressure demonstrated a direct linear relationship throughout the physiologic range, indicating lack of autoregulation. In contrast, in lambs two-weeks of age, surgical removal of one SCG resulted in ipsilateral loss of autoregulation during pronounced hypertension. Electrical stimulation of one SCG elicited unilateral increases in cerebral resistance to blood flow in both pre-term and two-week-old lambs, indicating functioning neural pathways in the instrumented, anesthetized lambs. We conclude cerebral autoregulation is non-functional in preterm lambs following cesarean delivery. Adrenergic control of cerebral vascular resistance becomes effective in newborn lambs within two-weeks after birth but SCG-dependent autoregulation is essential only during pronounced hypertension, well above the normal range of blood pressure.

Optimizing the Dose of Erythropoietin Required to Prevent Acute Ventilation-Induced Cerebral White Matter Injury in Preterm Lambs

“…Importantly, we have shown that the lamb brain at this gestational age is still susceptible to brain inflammation and white matter damage from ventilation [5,6,18] . Further, cerebral autoregulation has been shown to be impaired in preterm ventilated lambs of this age [51] . We believe that early EPO administration is necessary to target pathways of VIBI and prevent injury manifestation.…”

Developmental Maturation and Alpha-1 Adrenergic Receptors-Mediated Gene Expression Changes in Ovine Middle Cerebral Arteries

“…Alpha1ARs are the major regulator of norepinephrine-mediated vascular regulation 28 , 38 , 57 . With developmental maturation, the adrenergic system undergoes significant changes, which play an important role in CBF regulation and cellular/vascular growth including angiogenesis 21 , 22 , 26 , 38 , 57 , 59 – 61 . In our previous studies, we have demonstrated that the premature fetus lacks the sympathetic system-mediated regulation of CBF 26 .…”

“…Some have argued that the sympathetic system has a little biological significance in cerebral vasculature 24 , 25 . In contrast, evidence, particularly in a developing organism, supports a dynamic role in cerebrovascular autoregulation in response to changes in blood pressure 26 – 29 , and in the maintenance of cerebrovascular tone 30 . An important barrier towards the study of the role of norepinephrine was its inability to cross the blood-brain barrier 16 .…”

“…Similarly, in a term newborn lambs, removal of SCG was associated with linear increase in CBF with increase in mean arterial blood pressure. However, with intact SCG innervation, when mean arterial blood pressure was increased, CBF and O2 consumption remained constant 26 . In contrast, in a preterm lamb, even with intact SCG, CBF increased linearly with increase in mean arterial blood pressure indicating that sympathetic system in not fully mature at this stage 26 .…”

“…However, with intact SCG innervation, when mean arterial blood pressure was increased, CBF and O2 consumption remained constant 26 . In contrast, in a preterm lamb, even with intact SCG, CBF increased linearly with increase in mean arterial blood pressure indicating that sympathetic system in not fully mature at this stage 26 . Furthermore, others and we have reported that cerebrovascular reactivity, including that of alpha1-adrenergic-mechanisms, change dramatically with maturational development 26 , 38 , 42 , 43 , 49 .…”