Cervical spinal injury compromises caudal spinal tissue oxygenation and undermines acute intermittent hypoxia-induced phrenic long-term facilitation.
Cervical spinal injury compromises caudal spinal tissue oxygenation and undermines acute intermittent hypoxia-induced phrenic long-term facilitation.
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DOI：
10.1016/j.expneurol.2021.113726
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发表时间：
2021-08
影响因子：
5.3
通讯作者：
Mitchell GS
中科院分区：
文献类型：
--
作者：
Perim RR;Gonzalez-Rothi EJ;Mitchell GS
膈神经长时程易化（phrenic long-term facilitation，pLTF）是呼吸运动可塑性的一个重要模型，是急性间歇性缺氧（acute intermittent hypoxia，AIH）后膈神经爆发波振幅的持续增加。中度AIH通过一种被称为膈运动易化的Q通路的降钙素依赖性机制来增加pLTF。相反，严重AIH（严重低氧血症）增加脊髓腺苷积累并激活膈运动神经元腺苷2A受体，从而启动称为S通路的独特可塑性机制。由于Q和S途径通过相互串扰抑制相互作用，因此脊髓5-羟色胺释放和腺苷积累之间的平衡是重要的pLTF调节剂。脊髓损伤会降低损伤尾侧的脊髓组织氧分压（PtO2）。由于AIH正在探索作为一种神经治疗，以恢复颈椎损伤后的呼吸能力，我们测试的假设，减少PtO2在膈运动核后C2脊髓半切（C2Hx）破坏中度AIH诱导的pLTF，可能是由于在腺苷/5-羟色胺平衡的变化。我们记录C3/4腹侧颈PtO2与光电二极管，和双侧膈神经活动麻醉，麻痹和通气大鼠，有和没有C2Hx。在完整的大鼠中，PtO2在重度AIH期间低于中度AIH。在慢性C2Hx大鼠（损伤后> 8周）中，PtO2在基线和中度缺氧发作期间较低，接近完整大鼠中的严重AIH水平。C2Hx后，同侧pLTF变钝，但对侧观察到损伤。我们的结论是，C2Hx妥协PtO2附近的膈运动核和破坏pLTF，大概是由于在缺氧发作期间的5-羟色胺与腺苷平衡的转变。这些发现对于我们在慢性颈椎损伤患者中通过治疗性AIH恢复呼吸能力的努力中优化AIH方案具有重要意义。
An important model of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a persistent increase in phrenic burst amplitude following acute intermittent hypoxia (AIH). Moderate AIH elicits pLTF by a serotonin-dependent mechanism known as the Q pathway to phrenic motor facilitation. In contrast, severe AIH (greater hypoxemia) increases spinal adenosine accumulation and activates phrenic motor neuron adenosine 2A receptors, thereby initiating a distinct mechanism of plasticity known as the S pathway. Since the Q and S pathways interact via mutual cross-talk inhibition, the balance between spinal serotonin release and adenosine accumulation is an important pLTF regulator. Spinal injury decreases spinal tissue oxygen pressure (PtO2) caudal to injury. Since AIH is being explored as a neurotherapeutic to restore breathing ability after cervical spinal injury, we tested the hypothesis that decreased PtO2 in the phrenic motor nucleus after C2 spinal hemisection (C2Hx) undermines moderate AIH-induced pLTF, likely due to shifts in the adenosine/serotonin balance. We recorded C3/4 ventral cervical PtO2 with an optode, and bilateral phrenic nerve activity in anesthetized, paralyzed and ventilated rats, with and without C2Hx. In intact rats, PtO2 was lower during severe versus moderate AIH as expected. In chronic C2Hx rats (> 8 weeks post-injury), PtO2 was lower during baseline and moderate hypoxic episodes, approaching severe AIH levels in intact rats. After C2Hx, pLTF was blunted ipsilateral, but observed contralateral to injury. We conclude that C2Hx compromises PtO2 near the phrenic motor nucleus and undermines pLTF, presumably due to a shift in the serotonin versus adenosine balance during hypoxic episodes. These findings have important implications for optimizing AIH protocols in our efforts to restore breathing ability with therapeutic AIH in people with chronic cervical spinal injury.
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影响因子：
82.9
作者：
Li Y;Lucas-Osma AM;Black S;Bandet MV;Stephens MJ;Vavrek R;Sanelli L;Fenrich KK;Di Narzo AF;Dracheva S;Winship IR;Fouad K;Bennett DJ
通讯作者：
Bennett DJ
影响因子：
5.3
作者：
Doperalski, N. J.;Fuller, D. D.
通讯作者：
Fuller, D. D.
影响因子：
12.7
作者：
Cheng J;Korte N;Nortley R;Sethi H;Tang Y;Attwell D
通讯作者：
Attwell D
DOI：
10.1016/0034-5687(80)90113-9
发表时间：
1980-01-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
MILLHORN, DE;ELDRIDGE, FL;WALDROP, TG
通讯作者：
WALDROP, TG
影响因子：
8.3
作者：
GRUBB, RL;RAICHLE, ME;TERPOGOS.MM
通讯作者：
TERPOGOS.MM