Abstract
Objective: Repetitive umbilical cord occlusions (UCOs) in ovine fetus leading to severe acidemia result in adaptive shut-down of electrocortical activity [electrocorticogram (ECoG)] as well as systemic and brain inflammation. We hypothesized that the fetuses with earlier ECoG shut-down as a neuroprotective mechanism in response to repetitive UCOs will show less brain inflammation and, moreover, that chronic hypoxia will impact this relationship.Methods: Near-term fetal sheep were chronically instrumented with ECoG leads, vascular catheters, and a cord occluder and then underwent repetitive UCOs for up to 4 h or until fetal arterial pH was <7.00. Eight animals, hypoxic prior to the UCOs (SaO2 <55%), were allowed to recover 24 h post insult, while 14 animals, 5 of whom also were chronically hypoxic, were allowed to recover 48 h post insult, after which brains were perfusion-fixed. Time of ECoG shut-down and corresponding pH were noted, as well as time to then reach pH <7.00 (ΔT). Microglia (MG) were counted as a measure of inflammation in gray matter layers 4–6 (GM4–6) where most ECoG activity is generated. Results are reported as mean ± SEM for p < 0.05.Results: Repetitive UCOs resulted in worsening acidosis over 3–4 h with arterial pH decreasing to 6.97 ± 0.02 all UCO groups’ animals, recovering to baseline by 24 h. ECoG shut-down occurred 52 ± 7 min before reaching pH <7.00 at pH 7.23 ± 0.02 across the animal groups. MG counts were inversely correlated to ΔT in 24 h recovery animals (R = −0.84), as expected. This was not the case in normoxic 48 h recovery animals, and, surprisingly, in hypoxic 48 h recovery animals, this relationship was reversed (R = 0.90).Conclusion: Adaptive brain shut-down during labor-like worsening acidemia counteracts neuroinflammation in a hypoxia- and time-dependent manner.
Highlights
Human clinical studies with umbilical cord blood gas and pH assessment at birth indicate an increasing risk for neonatal adverse outcome and longer-term sequellae including cerebral palsy with pH values
Fetal acid–base status, cardiovascular parameters fetal heart rate (FHR) and arterial blood pressure (ABP) as well as ECoG amplitudes were within physiological range in all groups except for a lower baseline ECoG amplitude in H/umbilical cord occlusions (UCOs) 24 compared to the N/UCO 48 (Tables 1 and 2)
BRAIN AND CARDIOVASCULAR RESPONSES TO THE REPETITIVE UMBILICAL CORD OCCLUSIONS Repetitive UCOs resulted in worsening acidosis over 3–4 h with arterial pH decreasing from an average pH of 7.35 ± 0.01 at baseline to an average of 6.97 ± 0.02 across the groups and with all animals recovering to baseline by 24 h (Table 1) [12, 18]
Summary
Human clinical studies with umbilical cord blood gas and pH assessment at birth indicate an increasing risk for neonatal adverse outcome and longer-term sequellae including cerebral palsy with pH values
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