Dopamine protects cerebral autoregulation and prevents hippocampal necrosis after traumatic brain injury via block of ERK MAPK in juvenile pigs.
Dopamine protects cerebral autoregulation and prevents hippocampal necrosis after traumatic brain injury via block of ERK MAPK in juvenile pigs.
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DOI：
10.1016/j.brainres.2017.06.010
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发表时间：
2017-09-01
期刊：
影响因子：
2.9
通讯作者：
Armstead WM
中科院分区：
文献类型：
--
作者：
Curvello V;Hekierski H;Pastor P;Vavilala MS;Armstead WM
创伤性脑损伤（TBI）有助于儿童的发病率，更多的男孩经历TBI。脑外伤后，脑自动调节功能受损，导致预后不良。脑灌注压（CPP）通常通过使用血管活性药物增加平均动脉压（MAP）来恢复正常。在之前的研究中，新生和幼年猪，血管活性药物的选择影响TBI后的结果作为年龄和性别的函数，没有保护脑自动调节在两个年龄和性别。多巴胺（DA）通过抑制液压冲击伤（FPI）后ERK丝裂原活化蛋白激酶（MAPK）的上调来预防雄性和雌性新生猪脑自动调节的损害。我们研究了DA是否能保护幼年猪FPI后的自动调节和限制组织病理学以及ERK在该结果中的作用。结果表明，DA保护FPI后雄性和雌性幼猪的自动调节。FPI和DA对罂粟碱诱导的海马扩张无明显影响，DA可抑制ERK MAPK的活性，防止FPI后雄性和雌性海马CA1和CA3区神经元的丢失。这些数据表明，DA保护自动调节和限制海马神经元细胞坏死，通过阻断ERK后FPI在男性和女性的幼年猪。在之前研究的血管活性药物中，包括去甲肾上腺素、肾上腺素和苯肾上腺素，DA是唯一一种在性别和年龄上都能改善TBI后结局的药物。这些数据表明，DA应被视为一线治疗，以保护脑自动调节和促进脑的结果在儿童TBI，无论年龄和性别。
Traumatic brain injury (TBI) contributes to morbidity in children, and more boys experience TBI. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP). In prior studies of newborn and juvenile pigs, vasoactive agent choice influenced outcome after TBI as a function of age and sex, with none protecting cerebral autoregulation in both ages and sexes. Dopamine (DA) prevents impairment of cerebral autoregulation in male and female newborn pigs via inhibition of upregulation of ERK mitogen activated protein kinase (MAPK) after fluid percussion injury (FPI). We investigated whether DA protects autoregulation and limits histopathology after FPI in juvenile pigs and the role of ERK in that outcome. Results show that DA protects autoregulation in both male and female juvenile pigs after FPI. Papaverine induced dilation was unchanged by FPI and DA. DA blunted ERK MAPK and prevented loss of neurons in CA1 and CA3 hippocampus of males and females after FPI. These data indicate that DA protects autoregulation and limits hippocampal neuronal cell necrosis via block of ERK after FPI in male and female juvenile pigs. Of the vasoactive agents prior investigated, including norepinephrine, epinephrine, and phenylephrine, DA is the only one demonstrated to improve outcome after TBI in both sexes and ages. These data suggest that DA should be considered as a first line treatment to protect cerebral autoregulation and promote cerebral outcomes in pediatric TBI irrespective of age and sex.
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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：
3.7
作者：
Sharma, Deepak;Bithal, Parmod K.;Vavilala, Monica S.
通讯作者：
Vavilala, Monica S.
影响因子：
2.9
作者：
Armstead, WM
通讯作者：
Armstead, WM
影响因子：
5.7
作者：
Ishikawa, Seiji;Ito, Hiroyuki;Makita, Koshi
通讯作者：
Makita, Koshi