CB2 receptor activation attenuates microcirculatory dysfunction during cerebral ischemic/reperfusion injury.
CB2 receptor activation attenuates microcirculatory dysfunction during cerebral ischemic/reperfusion injury.
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DOI：
10.1016/j.mvr.2009.03.005
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发表时间：
2009-06
影响因子：
3.1
通讯作者：
Tuma RF
中科院分区：
文献类型：
--
作者：
Zhang M;Adler MW;Abood ME;Ganea D;Jallo J;Tuma RF
我们实验室之前的研究表明，选择性大麻素CB2激动剂能够减轻脑缺血/再灌注（I/R）损伤。本研究的目的是进一步测试这种衰减是否涉及I/R损伤期间的脑微循环功能。雄性小鼠进行大脑中动脉闭塞再灌注（MCAO/R）。选择性CB2激动剂以不同剂量和不同时间给予。在体内和体外检测脑梗死体积、神经功能和脑微循环功能（白细胞/内皮相互作用、细胞粘附分子表达和血脑屏障破坏）。CB2敲除小鼠按照相同的程序进行MCAO/R。与其他给药组和对照组相比，中剂量CB2激动剂在减轻脑梗死和改善神经功能方面效果最佳。在MCAO后3小时给予最佳剂量的CB2激动剂治疗仍然有效。短暂性缺血显著增加白细胞/内皮相互作用、粘附分子表达和血脑屏障破坏，这些都通过CB2激动剂预处理而减弱。CB2基因敲除小鼠脑梗死面积更大，神经功能更差。综上所述，脑I/R损伤时，CB2激活通过减弱脑微循环功能障碍起到保护脑的作用。
Previous studies from our laboratory indicated that selective cannabinoid CB2 agonists were able to attenuate cerebral ischemia/reperfusion (I/R) injury. The goal of current study is to further test whether this attenuation involves cerebral microcirculatory function during I/R injury. Middle cerebral artery occlusion with reperfusion (MCAO/R) was performed in male mice. A selective CB2 agonist was administered at different dosages and different times. Cerebral infarction volume, neurological function and cerebral microcirculatory function (leukocyte/endothelial interactions, cell adhesion molecule expression and blood-brain barrier disruption) were examined in vivo and in vitro. CB2 knockout mice were subjected to MCAO/R following same procedures. Administration of the CB2 agonist at middle dosage exerted optimal effects in reducing cerebral infarction and improving neurological function compared with other dosage groups and control group. Treatment with the CB2 agonist at the optimal dose was still effective when given 3 h after MCAO. Transient ischemia significantly increased leukocyte/endothelial interactions, adhesion molecules expression and blood-brain barrier disruption which were all attenuated by pre-treatment with a CB2 agonist. CB2 knockout mice showed larger cerebral infarction and worse neurological function compared to wide type. In conclusion, CB2 activation contributed to protecting the brain through the attenuation of cerebral microcirculatory dysfunction during cerebral I/R injury.
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DOI：
10.1016/j.molbrainres.2004.08.025
发表时间：
2004-12-06
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Golech, SA;McCarron, RM;Spatz, M
通讯作者：
Spatz, M
影响因子：
3.8
作者：
HEINEL, LA;RUBIN, S;TUMA, RF
通讯作者：
TUMA, RF
影响因子：
2.9
作者：
Belayev, L;Busto, R;Ginsberg, MD
通讯作者：
Ginsberg, MD
影响因子：
3.3
作者：
Muthian, S;Rademacher, DJ;Hillard, CJ
通讯作者：
Hillard, CJ
影响因子：
7.3
作者：
Pegorini, S;Zani, A;Sala, M
通讯作者：
Sala, M