Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.
Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.
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发表时间：
2007
期刊：
影响因子：
6.1
通讯作者：
K. Hayakawa;K. Mishima;M. Nozako;M. Hazekawa;Ayumi Ogata;M. Fujioka;Kazuhiko Harada;Shohei Mishima;K. Orito;N. Egashira;K. Iwasaki;M. Fujiwara
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作者：
K. Hayakawa;K. Mishima;M. Nozako;M. Hazekawa;Ayumi Ogata;M. Fujioka;Kazuhiko Harada;Shohei Mishima;K. Orito;N. Egashira;K. Iwasaki;M. Fujiwara
δ（9）-四氢大麻酚（δ（9）-THC）是大麻的主要精神活性成分，据报道通过大麻素CB（1）受体起神经保护剂的作用。在这项研究中，Delta（9）-THC显著降低了4小时小鼠大脑中动脉闭塞小鼠模型中的梗死体积。δ（9）-THC的神经保护作用被大麻素CB（1）受体拮抗剂SR 141716和将动物升温至31 ℃完全消除。Delta（9）-THC显著降低直肠温度，SR 141716和升温至31 ℃也抑制了低温效应。脑缺血24 h后，Delta（9）-THC显著增加纹状体和皮质CB（1）受体的表达水平，但对下丘脑无明显影响。在4小时的脑缺血期间，升温至31 ℃并没有增加MCA闭塞小鼠纹状体和皮质CB（1）受体的表达。这些结果表明Delta（9）-THC的神经保护作用是通过CB（1）受体通过温度依赖性机制介导的。此外，升温至31 ℃可能通过抑制纹状体和皮层中CB（1）受体的增加而不是下丘脑中CB（1）受体的增加来减弱Delta（9）-THC的神经保护和降温作用，这可能提示Delta（9）-THC的一种新的体温调节机制。
Delta(9)-tetrahydrocannabinol (Delta(9)-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB(1) receptor. In this study, Delta(9)-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Delta(9)-THC was completely abolished by SR141716, cannabinoid CB(1) receptor antagonist, and by warming the animals to 31 degrees C. Delta(9)-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 degrees C. At 24 h after cerebral ischemia, Delta(9)-THC significantly increased the expression level of CB(1) receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 degrees C during 4 h cerebral ischemia did not increase the expression of CB(1) receptor at the striatum and cortex in MCA-occluded mice. These results show that the neuroprotective effect of Delta(9)-THC is mediated by a temperature-dependent mechanism via the CB(1) receptor. In addition, warming to 31 degrees C might attenuate both the neuroprotective and hypothermic effects of Delta(9)-THC through inhibiting the increase in CB(1) receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Delta(9)-THC.