Sex and age differences in phenylephrine mechanisms and outcomes after piglet brain injury.
Sex and age differences in phenylephrine mechanisms and outcomes after piglet brain injury.
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DOI：
10.1038/pr.2017.83
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发表时间：
2017-07
影响因子：
3.6
通讯作者：
Armstead WM
中科院分区：
文献类型：
--
作者：
Curvello V;Hekierski H;Riley J;Vavilala M;Armstead WM
创伤性脑损伤(TBI)是儿童损伤相关死亡的主要原因，男孩和4岁以下儿童的预后尤其差。颅脑损伤后，脑自动调节功能经常受损，导致预后不良。在先前对新生猪的研究中，苯肾上腺素(Phe)优先保护脑损伤后雌性而不是雄性的脑自我调节。我们假设，与新生猪相比，苯丙氨酸可防止脑外伤后的自我调节功能受损和组织损伤，无论性别还是年龄较大的猪。本实验测定了雄性和雌性幼猪在PHE后中度液压脑损伤(FPI)后的脑自动调节功能、脑脊液ERK和内皮素的含量以及组织病理学变化。男性受试者的自我调节能力比女性受试者更严重。Phe保护FPI后雌雄动物的自身调节，阻断ERK和ET，并减少FPI后男性和女性的坏死神经元数量。这些数据表明，苯丙氨酸通过阻断ERK和内皮素来保护男性和女性FPI后的自我调节和限制神经元坏死。结合先前在新生猪中观察到的Phe保护雌性受试者而不是男性受试者的自我调节，这些数据表明，使用Phe来改善脑外伤后的预后既与性别有关，也与年龄有关。
Traumatic brain injury (TBI) is the leading cause of injury related death in children, with boys and children under 4 having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. In prior studies of newborn pigs, phenylephrine (Phe) preferentially protected cerebral autoregulation in females but not males after TBI. We hypothesized that, in contrast to the newborn, Phe prevents impairment of autoregulation and tissue injury following TBI in both sexes of older pigs. Cerebral autoregulation, CSF ERK and endothelin, and histopathology were determined after moderate fluid percussion brain injury (FPI) in male and female juvenile pigs after Phe. Autoregulation was more impaired in male subjects than females. Phe protects autoregulation in both sexes after FPI, blocked ERK and endothelin, and decreased the number of necrotic neurons in males and females after FPI. These data indicate that Phe protects autoregulation and limits neuronal necrosis via block of ERK and endothelin after FPI in maleas and females. Together with prior observations in newborn pigs where Phe protected autoregulation in female but not male subjects, these data suggest that use of Phe to improve outcome after TBI is both sex and age dependent.
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DOI：
10.1097/pcc.0000000000000603
发表时间：
2016-03
期刊：
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
影响因子：
--
作者：
Armstead WM;Riley J;Vavilala MS
通讯作者：
Vavilala MS
影响因子：
5.7
作者：
Girling, KJ;Cavill, G;Mahajan, RP
通讯作者：
Mahajan, RP
影响因子：
5.7
作者：
Ishikawa, Seiji;Ito, Hiroyuki;Makita, Koshi
通讯作者：
Makita, Koshi
影响因子：
8.8
作者：
Steiner, LA;Johnston, AJ;Menon, DK
通讯作者：
Menon, DK
影响因子：
8.8
作者：
Armstead WM;Kiessling JW;Kofke WA;Vavilala MS
通讯作者：
Vavilala MS