Dopamine prevents impairment of autoregulation after traumatic brain injury in the newborn pig through inhibition of Up-regulation of endothelin-1 and extracellular signal-regulated kinase mitogen-activated protein kinase.
Dopamine prevents impairment of autoregulation after traumatic brain injury in the newborn pig through inhibition of Up-regulation of endothelin-1 and extracellular signal-regulated kinase mitogen-activated protein kinase.
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DOI：
10.1097/pcc.0b013e3182712b44
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发表时间：
2013-02
期刊：
影响因子：
--
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
创伤性脑损伤是儿童发病率的一个因素，男孩发病率过高。与雌性仔猪相比，TBI后雄性仔猪的自动调节受损更多，这是通过痉挛原ET-1和ERK有丝分裂原活化蛋白激酶（MAPK，3种激酶家族，ERK、p38和JNK）的性别依赖性上调实现的。平均动脉压（MAP）升高，导致脑灌注压（CPP）增加，通过苯丙氨酸（Phe），改善了TBI后的自我调节功能障碍，在雌性而不是雄性仔猪中，通过调节ET-1和ERK MAPK的上调，在雌性中被阻断，但在雄性中加重。我们假设，升压选择，以提高CPP是重要的，在改善脑血流动力学TBI后，多巴胺（DA）将防止损害的自动调节在男性和女性仔猪通过阻断ET-1和ERK MAPK。前瞻性、随机动物研究。大学实验室。新生（1-5日龄）猪。在装有闭合颅窗的小猪中，在产生侧向液压冲击脑损伤之前和之后测定CPP和软脑膜动脉直径。FPI后30 min给予DA（15 μg/Kg/min iv）。ELISA法检测脑脊液ERK MAPK活性。DA在两种性别中同等地增加CPP，并防止FPI后软脑膜动脉直径的性别依赖性减小。在低血压期间，雄性FPI后软脑膜动脉扩张的损失大于雌性仔猪，但DA在损伤后两种性别中同等地防止了这种损伤。ET-1和ERK MAPK的释放在FPI后雄性仔猪中比雌性仔猪更大，但DA也在FPI后的雄性和雌性仔猪中同等地阻断它们的上调。这些数据表明，DA是保护FPI后的自动调节在两种性别。这些观察结果提倡考虑开发基于性别的治疗方法，用于治疗儿科TBI的血流动力学后遗症。
TBI contributes to morbidity in children and boys are disproportionately represented. Autoregulation is impaired more in male compared to female piglets after TBI through sex dependent upregulation of the spasmogen ET-1 and ERK mitogen activated protein kinase (MAPK, a family of 3 kinases, ERK, p38 and JNK). Elevation of mean arterial pressure (MAP) leading to increased cerebral perfusion pressure (CPP) via phenylephrine (Phe) improves impairment of autoregulation after TBI in female but not male piglets through modulation of ET-1 and ERK MAPK upregulation, blocked in females, but aggravated in males. We hypothesized that pressor choice to elevate CPP is important in improving cerebral hemodynamics after TBI and that dopamine (DA) will prevent impairment of autoregulation in both male and female piglets through blockade of ET-1 and ERK MAPK. Prospective, randomized animal study. University laboratory. Newborn (1–5 day old) pigs. CPP and pial artery diameter were determined before and after lateral fluid percussion brain injury was produced in piglets equipped with a closed cranial window. DA (15 μg/Kg/min iv) was administered 30 min post FPI. CSF ERK MAPK was determined by ELISA. DA increased CPP equivalently in both sexes and prevented sex dependent reductions in pial artery diameter after FPI. Loss of pial artery dilation during hypotension was greater in male compared to female piglets after FPI, but DA prevented such impairment equivalently in both sexes post injury. ET-1 and ERK MAPK release was greater in male compared to female piglets after FPI, but DA also blocked their upregulation equivalently in male and female piglets after FPI. These data indicate that DA is protective of autoregulation after FPI in both sexes. These observations advocate for the consideration of development of sex based therapies for treatment of hemodynamic sequalae of pediatric TBI.