Santiago-Castañeda Cindy, Huerta de la Cruz Saúl, Martínez-Aguirre Christopher, Orozco-Suárez Sandra Adela, Rocha Luisa
Department of Pharmacobiology, Center for Research and Advanced Studies (CINVESTAV), Mexico City 14330, Mexico.
Unit for Medical Research in Neurological Diseases, Specialties Hospital, National Medical Center SXXI (CMN-SXXI), Mexico City 06720, Mexico.
Pharmaceutics. 2022 Aug 2;14(8):1609. doi: 10.3390/pharmaceutics14081609.
This study aimed to determine if orally administered cannabidiol (CBD) lessens the cortical over-release of glutamate induced by a severe traumatic brain injury (TBI) and facilitates functional recovery. The short-term experiment focused on identifying the optimal oral pretreatment of CBD. Male Wistar rats were pretreated with oral administration of CBD (50, 100, or 200 mg/kg) daily for 7 days. Then, extracellular glutamate concentration was estimated by cortical microdialysis before and immediately after a severe TBI. The long-term experiment focused on evaluating the effect of the optimal treatment of CBD (pre- vs. pre- and post-TBI) 30 days after trauma. Sensorimotor function, body weight, and mortality rate were evaluated. In the short term, TBI induced a high release of glutamate (738% ± 173%; p < 0.001 vs. basal). Oral pretreatment with CBD at all doses tested reduced glutamate concentration but with higher potency at when animals received 100 mg/kg (222 ± 33%, p < 0.01 vs. TBI), an effect associated with a lower mortality rate (22%, p < 0.001 vs. TBI). In the long-term experiment, the TBI group showed a high glutamate concentration (149% p < 0.01 vs. SHAM). In contrast, animals receiving the optimal treatment of CBD (pre- and pre/post-TBI) showed glutamate concentrations like the SHAM group (p > 0.05). This effect was associated with high sensorimotor function improvement. CBD pretreatment, but not pre-/post-treatment, induced a higher body weight gain (39% ± 2.7%, p < 0.01 vs. TBI) and lower mortality rate (22%, p < 0.01 vs. TBI). These results support that orally administered CBD reduces short- and long-term TBI-induced excitotoxicity and facilitated functional recovery. Indeed, pretreatment with CBD was sufficient to lessen the adverse sequelae of TBI.
本研究旨在确定口服大麻二酚（CBD）是否能减轻重度创伤性脑损伤（TBI）诱导的皮质谷氨酸过度释放，并促进功能恢复。短期实验着重于确定CBD的最佳口服预处理方案。雄性Wistar大鼠每日口服CBD（50、100或200mg/kg），持续7天进行预处理。然后，在重度TBI之前和之后立即通过皮质微透析估计细胞外谷氨酸浓度。长期实验着重于评估创伤后30天CBD最佳治疗方案（TBI前与TBI前及TBI后）的效果。评估感觉运动功能、体重和死亡率。在短期内，TBI诱导谷氨酸大量释放（738%±173%；与基础值相比，p<0.001）。所有测试剂量的CBD口服预处理均降低了谷氨酸浓度，但当动物接受100mg/kg时效力更高（222±33%，与TBI组相比，p<0.01），这一效果与较低的死亡率相关（22%，与TBI组相比，p<0.001）。在长期实验中，TBI组显示谷氨酸浓度较高（与假手术组相比，149%，p<0.01）。相比之下，接受CBD最佳治疗方案（TBI前及TBI前后）的动物显示谷氨酸浓度与假手术组相似（p>0.05）。这一效果与感觉运动功能的显著改善相关。CBD预处理而非TBI前/后处理诱导了更高的体重增加（39%±2.7%，与TBI组相比，p<0.01）和更低的死亡率（22%，与TBI组相比，p<0.01）。这些结果支持口服CBD可降低TBI诱导的短期和长期兴奋性毒性，并促进功能恢复。事实上，CBD预处理足以减轻TBI的不良后遗症。
