Tao Yihao, Tang Jun, Chen Qianwei, Guo Jing, Li Lin, Yang Liming, Feng Hua, Zhu Gang, Chen Zhi
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Brain Res. 2015 Mar 30;1602:127-35. doi: 10.1016/j.brainres.2015.01.025. Epub 2015 Jan 24.
Germinal matrix hemorrhage (GMH) is one of the most common and devastating cerebrovascular events that affect premature infants, resulting in a significant socioeconomic burden. However, GMH has been largely unpreventable, and clinical treatments are mostly inadequate. In the present study, we tested the hypothesis that JWH133, a selective CB2 receptor agonist, could attenuate brain injury and neurological deficits in a clostridial collagenase VII induced GMH model in seven-day-old (P7) S-D rat pups. Up to 1h post-injury, the administration of JWH133 (1mg/kg, intraperitoneal injection) significantly attenuated brain edema at 24h post-GMH, which was reversed by a selective CB2R antagonist, SR144528 (3mg/kg, intraperitoneal injection). Long-term brain morphology and neurofunctional outcomes were also improved. In contrast, JWH133 did not have a noticeable effect on the hematoma volume during the acute phase. These data also showed that microglia activation and inflammatory cytokine (TNF-α) release were significantly inhibited by JWH133 after GMH. This current study suggests a potential clinical utility for CB2R agonists as a potential therapy to reduce neurological injury and improve patient outcomes after GMH.
生发基质出血（GMH）是影响早产儿的最常见且极具破坏性的脑血管事件之一，会造成巨大的社会经济负担。然而，GMH在很大程度上无法预防，且临床治疗大多并不充分。在本研究中，我们验证了一种假设，即选择性CB2受体激动剂JWH133可减轻七日龄（P7）S-D大鼠幼崽在梭菌胶原酶VII诱导的GMH模型中的脑损伤和神经功能缺损。损伤后长达1小时，给予JWH133（1mg/kg，腹腔注射）可在GMH后24小时显著减轻脑水肿，而选择性CB2R拮抗剂SR144528（3mg/kg，腹腔注射）可逆转这种作用。长期的脑形态和神经功能结果也得到了改善。相比之下，JWH133在急性期对血肿体积没有明显影响。这些数据还表明，GMH后JWH133可显著抑制小胶质细胞活化和炎性细胞因子（TNF-α）释放。本研究表明，CB2R激动剂作为一种潜在疗法，在减少GMH后的神经损伤和改善患者预后方面具有潜在的临床应用价值。
