Ampakine pretreatment enables a single hypoxic episode to produce phrenic motor facilitation with no added benefit of additional episodes.
Ampakine pretreatment enables a single hypoxic episode to produce phrenic motor facilitation with no added benefit of additional episodes.
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安帕金预处理可以使单次缺氧发作产生膈运动促进，而无需额外的缺氧发作带来额外好处。
DOI：
10.1152/jn.00307.2021
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发表时间：
2021
影响因子：
2.5
通讯作者：
Fuller,DavidD
中科院分区：
文献类型：
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作者：
Thakre,PrajwalP;Sunshine,MichaelD;Fuller,DavidD
重复的短暂缺氧发作产生膈神经输出的持续增加，持续时间远远超过急性间歇性缺氧（AIH）暴露（即，膈长期促进作用; pLTF）。用ampakines（变构调节AMPA受体的药物）预处理，能够使单一短暂缺氧发作产生pLTF，缺氧后持续长达90分钟。在这里，我们测试的假设，安巴金预处理将提高pLTF的幅度引起的反复发作的缺氧。在麻醉、机械通气和迷走神经切断的成年雄性Sprague-Dawley大鼠中记录膈神经输出。初步实验表明，安巴金CX 717（15 mg/kg iv）引起膈神经吸气爆发振幅急性增加，2 min后达到基线（BL）的70 ± 48%（P= 0.01）。这种增加的爆发没有持续（60分钟时2 ± 32% BL，P= 0.9）。在单次等二氧化碳缺氧（5 min，= 44 ± 9mmHg）前2 min给予CX 717，膈神经爆发波幅易化（60 min时BL为96 ± 62%，P< 0.001）。然而，当在3次、5分钟缺氧发作（= 45 ± 6 mmHg）前2 min给予CX 717时，pLTF减弱，且未达到统计学显著性（24 ± 29%BL，P= 0.08）。在没有CX 717预处理的情况下，在三次（60 min时74 ± 33%BL，P< 0.001）但不是一次缺氧（60 min时1 ± 8%BL，P= 0.9）后观察到pLTF。我们的结论是，pLTF不增强时，安巴金预处理后，反复发作的缺氧。新&值得注意的是，用安巴金CX 717预处理创造了使急性中度缺氧引起膈运动易化的条件，但当安巴金预处理后是间歇性缺氧时，没有观察到这种反应。因此，在麻醉和脊髓完整的大鼠中，安巴金和一次缺氧的组合似乎是触发呼吸神经可塑性的理想选择。
Repeated short episodes of hypoxia produce a sustained increase in phrenic nerve output lasting well beyond acute intermittent hypoxia (AIH) exposure (i.e., phrenic long-term facilitation; pLTF). Pretreatment with ampakines, drugs which allosterically modulate AMPA receptors, enables a single brief episode of hypoxia to produce pLTF, lasting up to 90 min after hypoxia. Here, we tested the hypothesis that ampakine pretreatment would enhance the magnitude of pLTF evoked by repeated bouts of hypoxia. Phrenic nerve output was recorded in urethane-anesthetized, mechanically ventilated, and vagotomized adult male Sprague–Dawley rats. Initial experiments demonstrated that ampakine CX717 (15 mg/kg iv) caused an acute increase in phrenic nerve inspiratory burst amplitude reaching 70 ± 48% baseline (BL) after 2 min (P= 0.01). This increased bursting was not sustained (2 ± 32% BL at 60 min,P= 0.9). When CX717 was delivered 2 min before a single episode of isocapnic hypoxia (5 min,= 44 ± 9 mmHg), facilitation of phrenic nerve burst amplitude occurred (96 ± 62% BL at 60 min,P< 0.001). However, when CX717 was given 2 min before three, 5-min hypoxic episodes (= 45 ± 6 mmHg) pLTF was attenuated and did not reach statistical significance (24 ± 29% BL,P= 0.08). In the absence of CX717 pretreatment, pLTF was observed after three (74 ± 33% BL at 60 min,P< 0.001) but not one episode of hypoxia (1 ± 8% BL at 60 min,P= 0.9). We conclude that pLTF is not enhanced when ampakine pretreatment is followed by repeated bouts of hypoxia. Rather, the combination of ampakine and a single hypoxic episode appears to be ideal for producing sustained increase in phrenic motor output.NEW & NOTEWORTHYPretreatment with ampakine CX717 created conditions that enabled an acute bout of moderate hypoxia to evoke phrenic motor facilitation, but this response was not observed when ampakine pretreatment was followed by intermittent hypoxia. Thus, in anesthetized and spinal intact rats, the combination of ampakine and one bout of hypoxia appears ideal for triggering respiratory neuroplasticity.
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Ampakine CX717 增强间歇性缺氧引起的舌下长期促进作用。
影响因子：
2.5
作者：
Turner,SM;ElMallah,MK;Hoyt,AK;Greer,JJ;Fuller,DD
通讯作者：
Fuller,DD
影响因子：
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作者：
Dale-Nagle, Erica A.;Hoffman, Michael S.;MacFarlane, Peter M.;Mitchell, Gordon S.
通讯作者：
Mitchell, Gordon S.
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影响因子：
3.7
作者：
Lorier AR;Funk GD;Greer JJ
通讯作者：
Greer JJ