AUTHOR=Xu Alex , Durosier Lucien Daniel , Ross Michael G. , Hammond Robert , Richardson Bryan S. , Frasch Martin G. 

TITLE=Adaptive Brain Shut-Down Counteracts Neuroinflammation in the Near-Term Ovine Fetus

JOURNAL=Frontiers in Neurology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2014.00110

DOI=10.3389/fneur.2014.00110

ISSN=1664-2295

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> 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 &lt;7.00. Eight animals, hypoxic prior to the UCOs (SaO<sub>2</sub> &lt;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 &lt;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 <italic>p</italic> &lt; 0.05.</p><p><bold>Results:</bold> 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 &lt;7.00 at pH 7.23 ± 0.02 across the animal groups. MG counts were inversely correlated to Δ<italic>T</italic> in 24 h recovery animals (<italic>R</italic> = −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 (<italic>R</italic> = 0.90).</p><p><bold>Conclusion:</bold> Adaptive brain shut-down during labor-like worsening acidemia counteracts neuroinflammation in a hypoxia- and time-dependent manner.</p>