Despite the high incidence of traumatic brain injury (TBI), there is no universal treatment to safely treat patients. Blunt brain injuries destroy primary neural tissue that results in impaired perfusion, excessive release of glutamate, inflammation, excitotoxicity, and progressive secondary neuronal cell death. We hypothesized that administration of cannabidiol (CBD) directly to a brain contusion site, will optimize delivery to the injured tissue which will reduce local neural excitation and inflammation to spare neural tissue and improve neurological outcome following TBI. CBD was infused into a gelfoam matrix forming an implant (CBDi), then applied over the dura at the contusion site as well as delivered systemically by injection (CBD.IP). Post-injury administration of CBDi+IP greatly reduced defecation scores, lesion volume, the loss of neurons in the ipsilateral hippocampus, the number of injured neurons of the contralateral hippocampus, and reversed TBI-induced glial fibrillary acidic protein (GFAP) upregulation which was superior to either CBD.IP or CBDi treatment alone. Vestibulomotor performance on the beam-balance test was restored by 12 days post-TBI and sustained through 28 days. CBDi+IP treated rats exhibited preinjury levels of spontaneous alternation on the spontaneous alternation T-maze. In the object recognition test, they had greater mobility and exploration of novel objects compared to contusion or implant alone consistent with reduced anxiety and restored cognitive function. These results suggest that dual therapy by targeting the site of injury internally with a CBD-infused medical carrier followed by systemic supplementation may offer a more effective countermeasure than systemic or implant treatment alone for the deleterious effects of penetrating head wounds.

尽管外伤性脑损伤 (TBI) 的发生率很高，但没有通用的治疗方法可以安全地治疗患者。钝性脑损伤会破坏初级神经组织，导致灌注受损、谷氨酸盐过度释放、炎症、兴奋性毒性和进行性继发性神经元细胞死亡。我们假设将大麻二酚 (CBD) 直接施用到脑挫伤部位，将优化向受伤组织的递送，这将减少局部神经兴奋和炎症以保护神经组织并改善 TBI 后的神经学结果。将 CBD 注入明胶海绵基质中形成植入物 (CBDi)，然后将其涂在挫伤部位的硬脑膜上，并通过注射全身给药 (CBD.IP)。CBDi+IP 的损伤后给药大大降低了排便评分、病灶体积、同侧海马神经元的丢失，对侧海马神经元的损伤数量，以及逆转 TBI 诱导的胶质纤维酸性蛋白 (GFAP) 上调，这优于单独的 CBD.IP 或 CBDi 治疗。梁平衡测试中的前庭运动性能在 TBI 后 12 天恢复并持续 28 天。CBDi+IP 治疗的大鼠在自发交替 T 迷宫中表现出自发交替的损伤前水平。在物体识别测试中，与单独的挫伤或植入物相比，他们对新物体的移动性和探索性更强，与焦虑减少和认知功能恢复一致。