Salvinorin A administration after global cerebral hypoxia/ischemia preserves cerebrovascular autoregulation via kappa opioid receptor in piglets.
Salvinorin A administration after global cerebral hypoxia/ischemia preserves cerebrovascular autoregulation via kappa opioid receptor in piglets.
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DOI：
10.1371/journal.pone.0041724
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Wang Z;Ma N;Riley J;Armstead WM;Liu R
脑缺氧/缺血（HI）在围产期并不少见。如果发生，它可能导致终身持续的严重神经功能障碍。Salvinorin A是一种非阿片类Kappa阿片受体（KOR）选择性激动剂，有可能解决这种毁灭性的情况。我们已经证明，在HI之前施用鼠尾草素A通过KOR和细胞外信号调节激酶（ERK）途径两者保留软脑膜动脉自动调节功能。在本研究中，我们测试了HI后给予鼠尾草素A可以通过KOR和ERK途径保留脑自动调节的假设。在配备有颅窗的小猪中，在HI之前和HI之后1小时监测软脑膜动脉对高碳酸血症、低血压和异丙肾上腺素的反应。HI后进行4组给药。对照组给予DMSO（1 µl/kg，i. v.）HI后立即给药。两个鼠尾草素A处理组在24小时内给予鼠尾草素A（10 μg/kg，i. v.）分别于HI后0和30 min给药。第4组在HI后0分钟共同给予鼠尾草素A和KOR拮抗剂norbinaltorphimine（Nor-BIN，1 µM局部）（n = 5）。 软脑膜动脉对高碳酸血症和低血压的扩张反应在整体HI后受损，并且在HI后立即或30分钟用鼠尾草素A施用来保存。当给予nor-BIN时，自动调节的保留被废除。在HI前和HI后1小时测定脑脊液（CSF）中磷酸化ERK（pERK）/ERK的水平。HI后，pERK/ERK水平在DMSO对照组和鼠尾草素A和nor-BIN共施用组中均显著增加。仅用鼠尾草素A组未观察到pERK/ERK水平升高。HI后0和30分钟的鼠尾草素A给药通过κ阿片受体和ERK途径保留了软脑膜动脉对高碳酸血症和低血压的自动调节。
Cerebral hypoxia/ischemia (HI) is not uncommon during the perinatal period. If occurring, it can result in severe neurologic disabilities that persist throughout life. Salvinorin A, a non-opioid Kappa opioid receptors (KOR) selective agonist, has the potential to address this devastating situation. We have demonstrated that salvinorin A administration before HI, preserves pial artery autoregulative function through both the KOR and extracellular signal-regulated kinases (ERK) pathways. In the present study, we tested the hypothesis that administration of salvinorin A after HI could preserve cerebral autoregulation via KOR and ERK pathway. The response of the pial artery to hypercapnia, hypotension and isoproterenol were monitored before and 1 hour after HI in piglets equipped with a cranial window. Four groups of drug administration were performed after HI. The control group had DMSO (1 µl/kg, i.v.) administrated immediately after HI. Two salvinorin A treated groups had salvinorin A (10 µg/kg, i.v.) administrated 0 and 30 min after HI, respectively. The 4th group had salvinorin A and the KOR antagonist norbinaltorphimine (Nor-BIN, 1 µM topical) co-administrated 0 min after HI (n = 5). The dilation responses of the pial artery to hypercapnia and hypotension were impaired after global HI and were preserved with salvinorin A administration immediately or 30 min after HI. The preservation of autoregulation was abolished when nor-BIN was administered. Levels of phosphor-ERK(pERK)/ERK in the cerebrospinal fluid (CSF) were measured before and 1 hour after HI. After HI, the pERK/ERK levels significantly increased in both DMSO control group and salvinorin A and nor-BIN co-administration group. The elevated levels of pERK/ERK were not observed with salvinorin A only groups. Salvinorin A administration 0 and 30 min after HI preserves autoregulation of pial artery to hypercapnia and hypotension via kappa opioid receptor and ERK pathway.
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UPA通过LRP和ERK MAPK损害缺氧/缺血后的脑炎。
影响因子：
2.9
作者：
Armstead, William M.;Cines, Douglas B.;Bdeir, Khalil;Kulikovskaya, Irina;Stein, Sherman C.;Higazi, Abd Al-Roof
通讯作者：
Higazi, Abd Al-Roof
影响因子：
2.5
作者：
Choi, Jeong-Sun;Kim, Ha-Young;Lee, Mun-Yong
通讯作者：
Lee, Mun-Yong
DOI：
10.1073/pnas.96.22.12866
发表时间：
1999-10-26
影响因子：
11.1
作者：
Alessandrini, A;Namura, S;Bonventre, JV
通讯作者：
Bonventre, JV
影响因子：
8.3
作者：
HALL, ED;PAZARA, KE
通讯作者：
PAZARA, KE
影响因子：
2.8
作者：
Mowry, M;Mosher, M;Briner, W
通讯作者：
Briner, W