The kappa opioid agonist niravoline decreases brain edema in the mouse middle cerebral artery occlusion model of stroke.
The kappa opioid agonist niravoline decreases brain edema in the mouse middle cerebral artery occlusion model of stroke.
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发表时间：
1997-07
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通讯作者：
C. Guéniau;C. Oberlander
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作者：
C. Guéniau;C. Oberlander
在清醒小鼠中，评估了Niravoline（RU 51599）（一种具有水利尿特性的κ阿片受体激动剂）与U 50488（另一种κ阿片受体激动剂）和甘露醇相比对缺血后脑水肿再吸收的影响。通过永久性闭塞右侧大脑中动脉获得缺血。闭塞后24小时，在脑含水量次最大时，收集血样以测量血清渗透压，并取出脑以测量对应于缺血核心和周边的两个额顶叶皮质组织样品的脑含水量。当在闭塞后20小时以3 - 30 mg/kg剂量单次腹腔注射给药时，niravoline显著降低了缺血组织外周的脑皮质含水量增加27%至48%。在这些相同剂量下，其使缺血小鼠的血清渗透压摩尔浓度增加至与非缺血小鼠相同的程度：4至10 mOsm/kg。U 50488通常表现出类似的活性。相比之下，甘露醇（1或2 g/kg，腹腔注射，闭塞后23小时）增加血清渗透压，但没有降低脑含水量。总之，κ阿片受体激动剂可以替代高渗药物治疗局灶性缺血型脑水肿，其使用仅限于脑水肿的早期阶段。
The effect of niravoline (RU 51599), a kappa opioid receptor agonist with water diuretic properties, was assessed on the resorption of postischemic cerebral edema in the conscious mouse in comparison with U 50488, another kappa opioid receptor agonist, and mannitol. Ischemia was obtained by permanent occlusion of the right middle cerebral artery. Twenty-four hours after occlusion, at a time when brain water content is submaximal, blood samples were collected to measure serum osmolality, and brains were removed to measure the brain water content of two samples of frontoparietal cortical tissue corresponding to the core and the periphery of ischemia. When administered from 3 to 30 mg/kg as a single i.p. injection 20 h after occlusion, niravoline significantly reduced the brain cortical water increase by 27% up to 48% in the periphery of the ischemic tissue. At these same doses, it increased the serum osmolality to the same extent in ischemic as in nonischemic mice: 4 to 10 mOsm/kg. U 50488 generally showed a similar activity. In contrast, mannitol (1 or 2 g/kg i.p. 23 h after occlusion) increased serum osmolality but did not decrease brain water content. In conclusion, kappa opiate agonists could be an alternative to hyperosmotic agents in the treatment of cerebral edema of the focal ischemia type, the use of which is limited to the early phase of cerebral edema.