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首页> 外文期刊>American Journal of Physiology >Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brain stem extracellular matrix formation
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Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brain stem extracellular matrix formation

机译：在脑干细胞外基质形成的关键窗口期间新生儿持续缺氧暴露后呼吸功能障碍

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The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined 7) whether there is a critical postnatal period of ECM expression in brain stem cardiorespiratory control regions and 2) whether the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia [SH (11% O_2, 24 h/day)] exposure is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus, hypoglossal motor nucleus, cuneate nucleus, and area postrema were immunofluorescently processed for aggrecan and Wisteria floribunda agglutinin (WFA), a key proteoglycan of the ECM and the perineuronal net. From postnatal day (P) 5 (P5), aggrecan and WFA expression increased postnatally in all regions. We observed an abrupt increase in aggrecan expression in the nTS, a region that integrates and receives afferent inputs from the carotid body, between P10 and P15 followed by a distinct and transient plateau between P15 and P20. WFA expression in the nTS exhibited an analogous transient plateau, but it occurred earlier (between P10 and P15). SH between Pll and P15 attenuated the HVR (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS, dorsal motor nucleus of the vagus, and area postrema. An intracisternal microinjection of chondroitinase ABC, an enzyme that digests chondroitin sulfate proteoglyeans, rescued the HVR and the increased aggrecan expression. These data indicate that important stages of ECM formation take place in key brain stem respiratory neural control regions and appear to be associated with a heightened vulnerability to hypoxia.
机译：细胞外基质（ECM）调节脑成熟，并在临界发展期间调节神经元可塑性起作用。我们检查了7）脑茎心肺控制区域中是否存在ECM表达的关键后期，2）是否在新生儿持续（5天）缺氧后的减毒缺氧通气反应（HVR）[SH（11％O_2，24小时/日）曝光与改变的ECM形成相关。晶氏菌菌菌（NTS），晶体，低缩略型电动机核，楔形核和面积Postrema的核泌尿菌菌（NTS），对Ecgecan和Wisteria Floribunda algglutinin（WFA），ECM的关键蛋白多糖和面向植物网的免疫加工。从后期（P）5（P5），在所有地区出现后，藻类和WFA表达增加。我们观察到NTS中的聚集体表达的突然增加，该区域整合并从颈动体之间接收来自颈动体的传入输入，然后在P10和P15之间，在P15和P20之间进行不同和瞬态的平台。 NTS中的WFA表达表现出类似的瞬态高原，但它之前发生（P10和P15之间）。 PLL和P15之间的SH衰减HVR（在P16评估），并增加了NTS，迷走的背部电机细胞核和面积postrema中的骨髓（但不是WFA）表达。软骨素酶ABC的脑内微调，一种消化硫酸软骨素蛋白质血糖蛋白血糖蛋白酶，拯救了HVR和增加的骨髓表达。这些数据表明ECM形成的重要阶段发生在关键脑干呼吸道神经控制区域中，并且似乎与对缺氧的高度脆弱性相关联。

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