Martinez-Vargas Marina, Morales-Gomez Julio, Gonzalez-Rivera Ruben, Hernandez-Enriquez Carla, Perez-Arredondo Adan, Estrada-Rojo Francisco, Navarro Luz
Physiology Department, School of Medicine, Universidad Nacional Autonoma de Mexico, AP 70-250, Mexico D.F. 04510, Mexico.
Int J Mol Sci. 2013 Nov 27;14(12):23341-55. doi: 10.3390/ijms141223341.
The endocannabinoid system is a component of the neuroprotective mechanisms that an organism displays after traumatic brain injury (TBI). A diurnal variation in several components of this system has been reported. This variation may influence the recovery and survival rate after TBI. We have previously reported that the recovery and survival rate of rats is higher if TBI occurs at 1:00 than at 13:00. This could be explained by a diurnal variation of the endocannabinoid system. Here, we describe the effects of anandamide administration in rats prior to the induction of TBI at two different times of the day: 1:00 and 13:00. We found that anandamide reduced the neurological damage at both times. Nevertheless, its effects on bleeding, survival, food intake, and body weight were dependent on the time of TBI. In addition, we analyzed the diurnal variation of the expression of the cannabinoid receptors CB1R and CB2R in the cerebral cortex of both control rats and rats subjected to TBI. We found that CB1R protein was expressed more during the day, whereas its mRNA level was higher during the night. We did not find a diurnal variation for the CB2R. In addition, we also found that TBI increased CB1R and CB2R in the contralateral hemisphere and disrupted the CB1R diurnal cycle.
内源性大麻素系统是生物体在创伤性脑损伤(TBI)后所展现的神经保护机制的一个组成部分。此前已有报道称该系统的几个组成部分存在昼夜变化。这种变化可能会影响TBI后的恢复情况和存活率。我们之前曾报道,若TBI发生在1点而非13点,大鼠的恢复率和存活率会更高。这可能是由内源性大麻素系统的昼夜变化所解释的。在此,我们描述了在一天中的两个不同时间点(1点和13点)对大鼠进行TBI诱导之前给予花生四烯酸乙醇胺的效果。我们发现,花生四烯酸乙醇胺在这两个时间点均能减轻神经损伤。然而,其对出血、存活、食物摄入量和体重的影响取决于TBI的时间。此外,我们分析了对照大鼠和遭受TBI的大鼠大脑皮质中大麻素受体CB1R和CB2R表达的昼夜变化。我们发现,CB1R蛋白在白天表达更多,而其mRNA水平在夜间更高。我们未发现CB2R存在昼夜变化。此外,我们还发现TBI会增加对侧半球中的CB1R和CB2R,并扰乱CB1R的昼夜周期。