Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets
Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets
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DOI：
10.1203/pdr.0b013e318186e5dd
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发表时间：
2008-12-01
影响因子：
3.6
通讯作者：
Martinez-Orgado, Jose
中科院分区：
文献类型：
--
作者：
Alvarez, Francisco J.;Lafuente, Hector;Martinez-Orgado, Jose
为了测试非精神活性大麻素大麻二酚（CBD）的神经保护作用，小猪在缺氧-缺血后接受静脉内CBD或媒介物（HI：两个颈动脉的暂时闭塞加上缺氧）。非缺氧缺血假手术仔猪作为对照。通过近红外光谱（NIRS）和振幅整合脑电图（aEEG）以及组织学评估（Nissl和FluoroJadeB染色）研究脑损伤。在HI+溶剂中，HI导致严重的脑血流动力学和代谢损伤，如NIBS中通过总Hb指数（THI）增加和组织氧合提取分数（FTOE）降低所反映的;在HI+CBD中，THI的增加变钝，FTOE保持与SHAM相似。HI显著降低EEG振幅，在HI+溶媒中未恢复，表明脑功能减退;在所有HI+溶媒中均观察到癫痫发作。然而，在HI+CBD中，EEG振幅恢复至46.4 +/-7.8%基线，并且仅在4/8头仔猪中出现癫痫发作（均p < 0.05）。在HI+载体中，存活神经元的数量减少，变性神经元的数量增加; CBD使这两种作用降低了50%以上。CBD给药没有副作用;此外，CBD给药与心脏，血液动力学和排泄有益作用相关。总之，HI后给予CBD可减少短期脑损伤，并与脑外益处相关。（Pediatr Res 64：653-658，2008）
To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia). Nonhypoxic-ischemic sham-operated piglets remained as controls. Brain damage was studied by near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography (aEEG) and by histologic assessment (Nissl and FluoroJadeB staining). In HI+vehicle, HI led to severe cerebral hemodynamic and metabolic impairment, as reflected in NIBS by an increase in total Hb index (THI) and a decrease in the fractional tissue oxygenation extraction (FTOE); in HI+CBD the increase of THI was blunted and FTOE remained similar to SHAM. HI profoundly decreased EEG amplitude, which was not recovered in HI+vehicle, indicating cerebral hypofunction; seizures were observed in all HI+vehicle. In HI+CBD, however, EEG amplitude recovered to 46.4 +/- 7.8% baseline and seizures appeared only in 4/8 piglets (both p < 0.05). The number of viable neurons decreased and that of degenerating neurons increased in HI+vehicle; CBD reduced both effects by more than 50%. CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects. In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits. (Pediatr Res 64: 653-658, 2008)