Maternal opioids age-dependently impair neonatal respiratory control networks.
Maternal opioids age-dependently impair neonatal respiratory control networks.
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DOI：
10.3389/fphys.2023.1109754
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发表时间：
2023
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
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在子宫内接触阿片类药物的婴儿是越来越多的临床人群，这些婴儿经常被诊断为新生儿戒断综合征（NAS）。NAS患儿有多种不良健康后果，包括呼吸窘迫。然而，许多因素导致NAS，混淆了理解母体阿片类药物如何直接影响新生儿呼吸系统的能力。呼吸是由脑干和脊髓的呼吸网络集中控制的，但母体阿片类药物对围产期呼吸网络发育的影响尚未研究。使用逐渐隔离的呼吸网络电路，我们测试了母体阿片类药物直接损害新生儿中枢呼吸控制网络的假设。在更完整的呼吸网络（脑干和脊髓）中，新生儿服用阿片类药物后，来自孤立中枢呼吸网络的虚拟呼吸相关运动活动受到年龄依赖性损害，但在更孤立的网络（含有preBötzinger复合物的髓质片）中不受影响。这些缺陷部分是由于出生后新生儿呼吸控制网络中残留的阿片类药物，并涉及呼吸模式的持久损伤。由于阿片类药物通常给予NAS患儿以抑制戒断症状，并且我们之前的工作证明了阿片类药物引起的新生儿呼吸抑制的急性钝化，我们进一步测试了孤立网络对外源性阿片类药物的反应。孤立的呼吸控制网络也显示出对外源性阿片样物质的年龄依赖性迟钝反应，这与主要呼吸节律产生区域preBötzinger复合物内阿片样物质受体表达的变化有关。因此，母体阿片类药物的年龄依赖性损害了新生儿中枢呼吸控制和对外源性阿片类药物的反应，表明中枢呼吸损伤有助于母体阿片类药物后新生儿呼吸不稳定，并可能导致NAS婴儿的呼吸窘迫。这些研究代表了我们对母体阿片类药物的复杂影响的理解取得了重大进展，即使在妊娠后期，也会导致新生儿呼吸障碍，这是开发支持NAS婴儿呼吸的新疗法的必要的第一步。
Infants exposed to opioids in utero are an increasing clinical population and these infants are often diagnosed with Neonatal Abstinence Syndrome (NAS). Infants with NAS have diverse negative health consequences, including respiratory distress. However, many factors contribute to NAS, confounding the ability to understand how maternal opioids directly impact the neonatal respiratory system. Breathing is controlled centrally by respiratory networks in the brainstem and spinal cord, but the impact of maternal opioids on developing perinatal respiratory networks has not been studied. Using progressively more isolated respiratory network circuitry, we tested the hypothesis that maternal opioids directly impair neonatal central respiratory control networks. Fictive respiratory-related motor activity from isolated central respiratory networks was age-dependently impaired in neonates after maternal opioids within more complete respiratory networks (brainstem and spinal cords), but unaffected in more isolated networks (medullary slices containing the preBötzinger Complex). These deficits were due, in part, to lingering opioids within neonatal respiratory control networks immediately after birth and involved lasting impairments to respiratory pattern. Since opioids are routinely given to infants with NAS to curb withdrawal symptoms and our previous work demonstrated acute blunting of opioid-induced respiratory depression in neonatal breathing, we further tested the responses of isolated networks to exogenous opioids. Isolated respiratory control networks also demonstrated age-dependent blunted responses to exogenous opioids that correlated with changes in opioid receptor expression within a primary respiratory rhythm generating region, the preBötzinger Complex. Thus, maternal opioids age-dependently impair neonatal central respiratory control and responses to exogenous opioids, suggesting central respiratory impairments contribute to neonatal breathing destabilization after maternal opioids and likely contribute to respiratory distress in infants with NAS. These studies represent a significant advancement of our understanding of the complex effects of maternal opioids, even late in gestation, contributing to neonatal breathing deficits, necessary first steps in developing novel therapeutics to support breathing in infants with NAS.
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DOI：
10.3390/ijerph18010232
发表时间：
2020-12-30
影响因子：
--
作者：
Batra K;Cruz P;Cross CL;Bhandari N;Abdulla F;Pharr JR;Buttner MP
通讯作者：
Buttner MP
影响因子：
2.3
作者：
Cinelli, Elenia;Bongianni, Fulvia;Mutolo, Donatella
通讯作者：
Mutolo, Donatella
影响因子：
2.5
作者：
Dubois, Christophe J.;Pierrefiche, Olivier
通讯作者：
Pierrefiche, Olivier
影响因子：
7.3
作者：
Endoh, T
通讯作者：
Endoh, T
影响因子：
4.5
作者：
da Silva Junior, Carlos Aparecido;Patrone, Luis Gustavo A.;Gargaglioni, Luciane H.
通讯作者：
Gargaglioni, Luciane H.