Preferential Protection of Cerebral Autoregulation and Reduction of Hippocampal Necrosis With Norepinephrine After Traumatic Brain Injury in Female Piglets.
Preferential Protection of Cerebral Autoregulation and Reduction of Hippocampal Necrosis With Norepinephrine After Traumatic Brain Injury in Female Piglets.
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DOI：
10.1097/pcc.0000000000000603
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Vavilala MS
中科院分区：
文献类型：
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作者：
Armstead WM;Riley J;Vavilala MS
创伤性脑损伤（TBI）是儿童发病率的一个因素，男孩的发病率不成比例。脑外伤后，脑自动调节功能受损，导致预后不良。脑灌注压（CPP）通常通过使用血管加压药增加MAP来恢复正常。在先前的研究中，我们观察到苯乙醯胺预防雌性仔猪液压冲击伤（FPI）后的自动调节功能受损，但加重雄性仔猪的自动调节功能受损。相比之下，多巴胺阻止FPI后两种性别的自动调节受损，这表明升压选择影响结果。丝裂原活化蛋白激酶（MAPK）的ERK亚型在FPI后产生血流动力学损伤，但细胞因子IL-6的作用尚不清楚。我们研究了去甲肾上腺素（NE）是否性别依赖性地保护FPI后的自动调节和限制组织病理学以及ERK和IL-6在该结果中的作用。前瞻性、随机动物研究。大学实验室。新生（1-5日龄）猪。在FPI之前和之后，在配备有封闭的颅窗的仔猪中以及在用NE处理后，测定CPP、CBF和软脑膜动脉直径。ELISA法检测脑脊液ERK MAPK活性。NE不能保护FPI后雄性仔猪的自动调节或防止CBF减少，但能完全保护FPI后雌性仔猪的自动调节。FPI和NE对罂粟碱引起的血管扩张无明显影响。去甲肾上腺素可增加FPI后雄猪ERK MAPK的表达，但可阻断FPI后雌猪ERK MAPK的表达。NE通过ERK MAPK依赖性机制加重了雄性大鼠IL-6的上调，但阻断了FPI后雌性大鼠IL-6的上调。NE以ERK MAPK和IL-6依赖的方式增加FPI后雄性仔猪海马CA 1和CA 3区神经元的丢失，但防止FPI后雌性仔猪海马神经元的丢失。FPI后NE通过调节ERK MAPK和IL-6以性别依赖的方式保护自身调节并限制海马神经元细胞坏死。
Traumatic brain injury (TBI) contributes to morbidity in children and boys are disproportionately represented. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasopressors to increase MAP. In prior studies, we observed that phenylephrine prevented in female but exacerbated impairment of autoregulation in male piglets after fluid percussion injury (FPI). In contrast, dopamine prevented impairment of autoregulation in both sexes after FPI, suggesting that pressor choice impacts outcome. The ERK isoform of mitogen activated protein kinase (MAPK) produces hemodynamic impairment after FPI, but the role of the cytokine IL-6 is unknown. We investigated whether norepinephrine (NE) sex dependently protects autoregulation and limits histopathology after FPI and the role of ERK and IL-6 in that outcome. Prospective, randomized animal study. University laboratory. Newborn (1–5 day old) pigs. CPP, CBF, and pial artery diameter were determined before and after FPI in piglets equipped with a closed cranial window and post treated with NE. CSF ERK MAPK was determined by ELISA. NE does not protect autoregulation or prevent reduction in CBF in male but fully protects autoregulation in female piglets after FPI. Papaverine induced dilation was unchanged by FPI and NE. NE increased ERK MAPK upregulation in male but blocked such upregulation in female piglets after FPI. NE aggravated IL-6 upregulation in males in an ERK MAPK dependent mechanism but blocked IL-6 upregulation in females after FPI. NE augments loss of neurons in CA1 and CA3 hippocampus of male piglets after FPI in an ERK MAPK and IL-6 dependent manner, but prevents loss of neurons in females after FPI. NE protects autoregulation and limits hippocampal neuronal cell necrosis via modulation of ERK MAPK and IL-6 after FPI in a sex dependent manner.