K channel impairment determines sex and age differences in epinephrine-mediated outcomes after brain injury.
K channel impairment determines sex and age differences in epinephrine-mediated outcomes after brain injury.
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DOI：
10.1002/jnr.24063
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发表时间：
2017-10
影响因子：
4.2
通讯作者：
Vavilala MS
中科院分区：
文献类型：
--
作者：
Armstead WM;Riley J;Vavilala MS
创伤性脑损伤（TBI）是儿童损伤相关死亡的主要原因，其中男孩和4岁以下儿童的结局特别差。ATP和钙敏感性（Katp和Kca）通道的激活产生血管舒张，并有助于自动调节，两者在TBI后受损，导致不良结局。CNS损伤后丝裂原活化蛋白激酶的c-Jun末端激酶（JNK）亚型的上调导致K通道功能受损。血管活性剂可用于使脑灌注压正常化。肾上腺素（EPI）通过JNK的差异调节防止雌性和雄性新生儿和雌性幼年猪TBI后脑自动调节受损和海马神经元细胞坏死，但对雄性幼年猪无影响。本研究使用配备有闭合颅窗的麻醉猪来解决以下假设：差异性K通道损伤有助于脑损伤后EPI介导的结果的年龄和性别差异。结果显示，TBI后，响应于Katp和Kcan通道激动剂色满卡林和NS 1619的软脑膜动脉扩张受损，并且在雌性和雄性新生儿和雌性幼年猪中，但在雄性幼年猪中，EPI阻止了这种损伤。使用血管舒张作为功能指标，这些数据表明，EPI通过以年龄和性别依赖性方式阻断JNK来保护K通道功能，从而保护脑自动调节并限制TBI后的组织病理学。液压脑损伤（FPI）后，年轻和雄性猪的脑自动调节功能受损程度高于老年和雌性猪。K通道激动剂cromakalim的脑血管舒张有助于自动调节，并且与女性相比，男性在FPI后更钝。FPI后给予肾上腺素（EPI）使脑灌注压正常化，可通过阻断丝裂原活化蛋白激酶的JNK亚型，防止FPI后年轻男性和女性、老年女性（但非年轻男性）中色满卡林诱导的血管扩张受损。使用血管舒张作为功能指标，这些数据表明，EPI通过以年龄和性别依赖性方式阻断JNK来保护K通道功能，从而保护FPI后的脑自动调节。图的图例：克罗卡林对新生雄性和雌性猪以及幼年雄性和雌性猪在用EPI处理的FPI之前（假手术）、之后和之后的软脑膜动脉直径的影响。
Traumatic brain injury (TBI) is the leading cause of injury related death in children, with boys and children under 4 years having particularly poor outcomes. Activation of ATP and Calcium sensitive (Katp and Kca) channels produce cerebrovasodilation and contribute to autoregulation, both impaired after TBI, contributory to poor outcome. Upregulation of the c-Jun-terminal kinase (JNK) isoform of mitogen activated protein kinase produces K channel function impairment after CNS injury. Vasoactive agents can be used to normalize cerebral perfusion pressure. Epinephrine (EPI) prevents impairment of cerebral autoregulation and hippocampal neuronal cell necrosis after TBI in female and male newborn and female juvenile but not male juvenile pigs via differential modulation of JNK. The present study used anesthetized pigs equipped with a closed cranial window to address the hypothesis that differential K channel impairment contributes to age and sex differences in EPI-mediated outcomes after brain injury. Results show that pial artery dilation in response to the Katp and Kcan channel agonists cromakalim and NS 1619 was impaired after TBI and that such impairment was prevented by EPI in female and male newborn and female juvenile but not male juvenile pigs. Using vasodilation as an index of function, these data indicate that EPI protects cerebral autoregulation and limits histopathology after TBI through protection of K channel function via blockade of JNK in an age and sex dependent manner. Cerebral autoregulation is impaired more in young and male compared to older and female pigs after fluid percussion brain injury (FPI). Cerebrovasodilation to the K channel agonist cromakalim contributes to autoregulation and is blunted after FPI more in the male compared to the female. Epinephrine (EPI) administered after FPI to normalize cerebral perfusion pressure prevents impairment of cromakalim induced vaosodilation in young male and female, older female but not young male safter FPI via blockade of the JNK isoform of mitogen activated protein kinase. Using vasodilation as an index of function, these data indicate that EPI protects cerebral autoregulation after FPI through protection of K channel function via blockade of JNK in an age and sex dependent manner. Legend for Figure: Influence of cromakalim on pial artery diameter in newborn male and female pigs and in juvenile male and female pigs before (sham), after FPI, and after FPI treated with EPI.
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影响因子：
8.3
作者：
Armstead, WM
通讯作者：
Armstead, WM
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：
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
影响因子：
8.8
作者：
Steiner, LA;Johnston, AJ;Menon, DK
通讯作者：
Menon, DK