Impaired cerebral blood flow autoregulation during posttraumatic arterial hypotension after fluid percussion brain injury is prevented by phenylephrine in female but exacerbated in male piglets by extracellular signal-related kinase mitogen-activated protein kinase upregulation.
Impaired cerebral blood flow autoregulation during posttraumatic arterial hypotension after fluid percussion brain injury is prevented by phenylephrine in female but exacerbated in male piglets by extracellular signal-related kinase mitogen-activated protein kinase upregulation.
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DOI：
10.1097/ccm.0b013e3181e8ac1a
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发表时间：
2010-09
影响因子：
8.8
通讯作者：
Vavilala MS
中科院分区：
文献类型：
--
作者：
Armstead WM;Kiessling JW;Kofke WA;Vavilala MS
创伤性脑损伤 (TBI) 会导致儿童的发病率和死亡率，其中男孩的比例不成比例。低血压很常见，并且会使 TBI 后的预后恶化。仔猪液体冲击脑损伤 (FPI) 后，细胞外信号相关激酶 (ERK) 丝裂原激活蛋白激酶 (MAPK) 上调并减少 CBF。我们假设，通过去氧肾上腺素 (PHE) 增加 CPP，性别依赖性地通过调节 ERK MAPK，减少 FPI 后低血压期间大脑自动调节的损害。前瞻性随机动物研究。大学实验室。新生（1-5 天）猪。在正常血压和失血性低血压期间，对未治疗的、受伤前和受伤后的 PHE（1 μg/kg/min iv）治疗的雄性和雌性猪在 FPI 之前和之后测定 CBF、软脑膜动脉直径、ICP 和自动调节指数 (ARI)。 CSF ERK MAPK 通过 ELISA 测定。 FPI 后软脑膜动脉直径、CBF、CPP 和 ICP 的减少在男性中更大，而 FPI 前或后的 PHE 减弱了这些作用。在低血压和 FPI 期间，男性软脑膜动脉扩张受损更严重。 PHE 减少了女性 FPI 后低血压软脑膜动脉扩张的损害，但矛盾的是，男性 FPI 后 PHE 引起血管收缩。 FPI 和 PHE 未改变罂粟碱诱导的软脑膜动脉血管舒张作用。男性低血压时 CBF、CPP 和 ARI 显着下降，女性 FPI 下降较少。 PHE 可防止女性低血压期间 CBF、CPP 和 ARI 的减少，但会增加男性的减少。 FPI 后，男性 CSF ERK MAPK 的增加多于女性。 FPI 后，PHE 减弱了女性 ERK MAPK 的上调，但增加了男性 ERK MAPK 的上调。这些数据表明，PHE 引起的 CPP 升高可通过调节 ERK MAPK 来防止 FPI 后低血压期间大脑自动调节的损害。这些数据表明性别依赖性机制在儿童 TBI 后大脑自动调节中的潜在作用。
Traumatic brain injury (TBI) contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after TBI. Extracellular signal-related kinase (ERK) mitogen activated protein kinase (MAPK) is upregulated and reduces CBF after fluid percussion brain injury (FPI) in piglets. We hypothesized that increased CPP via phenylephrine (PHE) sex dependently reduces impairment of cerebral autoregulation during hypotension after FPI through modulation of ERK MAPK. Prospective, randomized animal study. University laboratory. Newborn (1–5 day old) pigs. CBF, pial artery diameter, ICP and autoregulatory index (ARI) were determined before and after FPI in untreated, pre- and post-injury PHE (1 μg/kg/min iv) treated male and female pigs during normotension and hemorrhagic hypotension. CSF ERK MAPK was determined by ELISA. Reductions in pial artery diameter, CBF, CPP and elevated ICP after FPI were greater in males, which were blunted by PHE pre- or post-FPI. During hypotension and FPI, pial artery dilation was impaired more in males. PHE decreased impairment of hypotensive pial artery dilation after FPI in females, but paradoxically caused vasoconstriction after FPI in males. Papaverine induced pial artery vasodilation was unchanged by FPI and PHE. CBF, CPP, and ARI decreased markedly during hypotension and FPI in males but less in females. PHE prevented reductions in CBF, CPP, and ARI during hypotension in females but increased reductions in males. CSF ERK MAPK was increased more in males than females after FPI. PHE blunted ERK MAPK upregulation in females, but increased ERK MAPK upregulation in males after FPI. These data indicate that elevation of CPP with PHE sex dependently prevents impairment of cerebral autoregulation during hypotension after FPI through modulation of ERK MAPK. These data suggest the potential role for sex dependent mechanisms in cerebral autoregulation after pediatric TBI.