James Haley VA Medical Center and University of South Florida, Tampa, Florida, USA.
Department of Neurology, University of South Florida, Tampa, Florida, USA.
Cannabis Cannabinoid Res. 2022 Aug;7(4):424-435. doi: 10.1089/can.2021.0053. Epub 2021 Nov 5.
Administration of the phytocannabinoid Δ-tetrahydrocannabinol (Δ-THC) will enhance brain repair and improve short-term spatial working memory in mice following controlled cortical impact (CCI) by upregulating granulocyte colony-stimulating factor (G-CSF) and other neurotrophic factors (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]) in hippocampus (HP), cerebral cortex, and striatum. C57BL/6J mice underwent CCI and were treated for 3 days with Δ-THC 3 mg/kg intraperitoneally (i.p.). Short-term working memory was determined using the spontaneous alternations test during exploratory behavior in a Y-maze. Locomotor function was measured as latency to fall from a rotating drum (rotometry). These behaviors were recorded at baseline and 3, 7, and 14 days after CCI. Groups of mice were euthanized at 7 and 14 days. Extent of microgliosis, astrocytosis, and G-CSF, BDNF, and GDNF expression were measured at 7 and 14 days in cerebral cortex, striatum, and HP on the side of the trauma. Levels of the most abundant endocannabinoid (2-arachidonoyl-glycerol [2-AG]) was also measured at these times. Δ-THC-treated mice exhibited marked improvement in performance on the Y-maze indicating that treatment with the phytocannabinoid could reverse the deficit in working memory caused by the CCI. Δ-THC-treated mice ran on the rotarod longer than vehicle-treated mice and recovered to normal rotarod performance levels at 2 weeks. Δ-THC-treated mice, compared with vehicle-treated animals, exhibited significant upregulation of G-CSF as well as BDNF and GDNF in the cerebral cortex, striatum, and HP. Levels of 2-AG were also increased in the Δ-THC-treated mice. Administration of the phytocannabinoid Δ-THC promotes significant functional recovery from traumatic brain injury (TBI) in the realms of working memory and locomotor function. This beneficial effect is associated with upregulation of brain 2-AG, G-CSF, BDNF, and GDNF. The latter three neurotrophic factors have been previously shown to mediate brain self-repair following TBI and stroke.
Administration of the phytocannabinoid Δ-tetrahydrocannabinol (Δ-THC) will enhance brain repair and improve short-term spatial working memory in mice following controlled cortical impact (CCI) by upregulating granulocyte colony-stimulating factor (G-CSF) and other neurotrophic factors (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]) in hippocampus (HP), cerebral cortex, and striatum.
植物大麻素 Δ-四氢大麻酚（Δ-THC）的给药通过上调粒细胞集落刺激因子（G-CSF）和其他神经营养因子（脑源性神经营养因子[BDNF]，胶质源性神经营养因子[GDNF]），增强大脑修复并改善控制皮质撞击（CCI）后小鼠的短期空间工作记忆海马体（HP）、大脑皮层和纹状体。
C57BL/6J 小鼠接受 CCI 并接受 3 天的 Δ-THC 3mg/kg 腹腔内（i.p.）治疗。使用 Y 迷宫中的自发交替测试来确定短期工作记忆。通过从旋转鼓（旋转计）上掉落的潜伏期来测量运动功能。这些行为在 CCI 后 3、7 和 14 天进行记录。在 7 天和 14 天，处死各组小鼠。在创伤侧的大脑皮层、纹状体和 HP 中测量了 7 天和 14 天时小胶质细胞增生、星形胶质细胞增生和 G-CSF、BDNF 和 GDNF 的表达。在这些时间点还测量了最丰富的内源性大麻素（2-花生四烯酰甘油[2-AG]）的水平。
与载体处理的小鼠相比，接受植物大麻素治疗的小鼠在 Y 迷宫上的表现明显改善，表明植物大麻素的治疗可以逆转 CCI 引起的工作记忆缺陷。接受 Δ-THC 治疗的小鼠在旋转棒上的运行时间长于接受载体治疗的小鼠，并且在 2 周时恢复到正常的旋转棒性能水平。与载体处理的动物相比，接受 Δ-THC 治疗的小鼠在大脑皮层、纹状体和 HP 中 G-CSF 以及 BDNF 和 GDNF 的表达明显上调。接受 Δ-THC 治疗的小鼠的 2-AG 水平也升高。
Administration of the phytocannabinoid Δ-THC promotes significant functional recovery from traumatic brain injury (TBI) in the realms of working memory and locomotor function. This beneficial effect is associated with upregulation of brain 2-AG, G-CSF, BDNF, and GDNF. The latter three neurotrophic factors have been previously shown to mediate brain self-repair following TBI and stroke.
Administration of the phytocannabinoid Δ-THC promotes significant functional recovery from traumatic brain injury (TBI) in the realms of working memory and locomotor function. This beneficial effect is associated with upregulation of brain 2-AG, G-CSF, BDNF, and GDNF. The latter three neurotrophic factors have been previously shown to mediate brain self-repair following TBI and stroke.
植物大麻素 Δ-THC 的给药可促进创伤性脑损伤（TBI）在工作记忆和运动功能领域的显著功能恢复。这种有益的效果与大脑 2-AG、G-CSF、BDNF 和 GDNF 的上调有关。这三个神经营养因子以前已经被证明可以介导 TBI 和中风后的大脑自我修复。
