Posttreatment but Not Pretreatment with Selective &bgr;-Adrenoreceptor 1 Antagonists Provides Neuroprotection in the Hippocampus in Rats Subjected to Transient Forebrain Ischemia
Posttreatment but Not Pretreatment with Selective &bgr;-Adrenoreceptor 1 Antagonists Provides Neuroprotection in the Hippocampus in Rats Subjected to Transient Forebrain Ischemia
复制标题
选择性后处理而非预处理
作者：
M. Iwata;S. Inoue;M. Kawaguchi;Mitsutoshi Nakamura;N. Konishi;H. Furuya
背景：β-肾上腺素受体拮抗剂提供针对局灶性脑缺血的神经保护作用，但这些拮抗剂对实验性全脑缺血的影响尚不清楚。也就是说，尚未研究缺血性损伤后脆弱大脑区域中β-肾上腺素受体拮抗作用的作用。因此，我们研究了缺血前或缺血后给予普萘洛尔（一种非选择性β-肾上腺素受体拮抗剂）、艾司洛尔和兰地洛尔（选择性β-肾上腺素受体1拮抗剂）对大鼠前脑缺血的神经保护作用。方法：雄性Sprague-Dawley大鼠在8分钟双侧给药前30分钟或给药后60分钟开始静脉注射生理盐水10μL·h−1、普萘洛尔100μg·kg−1·min−1、艾司洛尔200μg·kg−1·min−1或兰地洛尔50μg·kg−1·min−1。异氟烷 (1.5%) 麻醉下颈动脉闭塞合并低血压 (35 mm Hg)。所有药物均连续施用直至再灌注后5天，并在这5天后对动物进行神经学和组织学评估。结果：用普萘洛尔、艾司洛尔或兰地洛尔进行缺血前治疗未能提供针对海马前脑缺血的神经保护作用。接受普萘洛尔治疗的大鼠往往运动活动评分较差，死亡率较高（高达 64%），但与其他组的差异无统计学意义。使用艾司洛尔和兰地洛尔（但普萘洛尔）进行缺血后治疗可减少前脑缺血后的神经元损伤。然而，在用任何β-肾上腺素受体拮抗剂或盐水进行化学后处理的大鼠中，运动活动没有差异。结论：艾司洛尔和兰地洛尔缺血后治疗对双侧颈动脉闭塞合并失血性休克大鼠的海马提供神经保护作用，而普萘洛尔治疗未能显示出神经保护作用。我们认为，同时使用β-阻滞剂和电击可能会起到全身抑制剂的作用，而不是神经保护剂，从而导致脑缺血加剧。
BACKGROUND:&bgr;-Adrenoreceptor antagonists provide neuroprotection against focal cerebral ischemia, but the effects of these antagonists on experimental global cerebral ischemia are unknown. That is, the effect of &bgr;-adrenoreceptor antagonism in vulnerable brain regions after ischemic insult has not been examined. Therefore, we investigated the neuroprotective effects of preischemic or postischemic administration of propranolol (a nonselective &bgr;-adrenoreceptor antagonist), esmolol, and landiolol (selective &bgr;-adrenoreceptor 1 antagonists) against forebrain ischemia in rats. METHODS:IV administration of saline 10 &mgr;L · h−1, propranolol 100 &mgr;g · kg−1 · min−1, esmolol 200 &mgr;g · kg−1 · min−1, or landiolol 50 &mgr;g · kg−1 · min−1 in male Sprague-Dawley rats was started 30 minutes before or 60 minutes after 8-minute bilateral carotid artery occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. All drugs were administered continuously until 5 days after reperfusion, and the animals were evaluated neurologically and histologically after this 5-day period. RESULTS:Preischemic treatment with propranolol, esmolol, or landiolol failed to provide neuroprotection against forebrain ischemia in the hippocampus. Rats treated with propranolol tended to have a worse score for motor activity and a higher mortality rate (up to 64%), but the differences with other groups were not statistically significant. Postischemic treatment with esmolol and landiolol, but not with propranolol, reduced neuronal injury after forebrain ischemia. However, motor activity did not differ among rats treated postischemically with any of the &bgr;-adrenoreceptor antagonists or saline. CONCLUSIONS:Postischemic treatment with esmolol and landiolol provided neuroprotection in the hippocampus in rats subjected to bilateral carotid artery occlusion combined with hemorrhagic shock, whereas treatment with propranolol failed to show neuroprotection. We suggest that concomitant &bgr;-blockade and shock might work as a systemic depressant, rather than a neuroprotectant, resulting in exacerbation of cerebral ischemia.
β-肾上腺素受体拮抗剂可抑制暴露于旷场的大鼠的体温升高和血浆 IL-6 的增加。
影响因子：
4.1
作者：
Soszynski,D;Kozak,W;Conn,CA;Rudolph,K;Kluger,MJ
通讯作者：
Kluger,MJ
影响因子：
15.9
作者：
LeTulzo, Y;Shenkar, R;Abraham, E
通讯作者：
Abraham, E