Noninvasive Tracking of Anesthesia Neurotoxicity in the Developing Rodent Brain.
Noninvasive Tracking of Anesthesia Neurotoxicity in the Developing Rodent Brain.
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DOI：
10.1097/aln.0000000000002229
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发表时间：
2018-07
期刊：
影响因子：
8.8
通讯作者：
Benveniste H
中科院分区：
文献类型：
--
作者：
Makaryus R;Lee H;Robinson J;Enikolopov G;Benveniste H
Potential deleterious effect of multiple anesthesia exposures on the developing brain remains a clinical concern. We hypothesized that multiple neonatal anesthesia exposures are more detrimental to brain maturation than an equivalent single exposure, with more pronounced long-term behavioral consequences. We designed a translational approach using proton magnetic resonance spectroscopy (1HMRS) in rodents, noninvasively tracking the neuronal marker N-Acetyl-Aspartate (NAA), in addition to tracking behavioral outcomes. Trajectories of NAA in anesthesia naïve rats (n=62, post-natal day (PND) 5–35) were determined using 1HMRS, creating an “NAA growth chart.” This chart was used to compare the effects of a single six-hour sevoflurane exposure (PND7) to three two-hour exposures (PND5, 7, 10). Long-term effects on behavior were separately examined utilizing novel object recognition (NOR), open field testing (OFT), and Barnes maze tasks. Utilizing the NAA growth chart, deviations from the normal NAA trajectory were documented in both single and multiple exposure groups, with Z-scores (mean±SD) of −0.80±0.58 (p=0.003) and −1.87±0.58 (p=0.002), respectively. Behavioral testing revealed that, in comparison with unexposed and single exposed, multiple exposed animals spent the least time with the novel object in NOR (F(2,44)=4.65, p=0.015), travelled the least distance in OFT (F(2,57)=4.44, p=0.016), but exhibited no learning deficits in the Barnes maze. Our data demonstrate the feasibility of using the biomarker NAA, measured noninvasively using 1HMRS, for longitudinally monitoring anesthesia-induced neurotoxicity. These results also indicate that the neonatal rodent brain is more vulnerable to multiple anesthesia exposures than to a single exposure of the same cumulative duration.
