当前位置: X-MOL 学术Bioeng. Transl. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Systemic administration of dendrimer N-acetyl cysteine improves outcomes and survival following cardiac arrest
Bioengineering & Translational Medicine ( IF 7.4 ) Pub Date : 2021-09-14 , DOI: 10.1002/btm2.10259
Hiren R Modi 1, 2 , Qihong Wang 1, 3 , Sarah J Olmstead 4 , Elizabeth S Khoury 4 , Nirnath Sah 4 , Yu Guo 1 , Payam Gharibani 5 , Rishi Sharma 6 , Rangaramanujam M Kannan 6 , Sujatha Kannan 4 , Nitish V Thakor 1
Affiliation  

Cardiac arrest (CA), the sudden cessation of effective cardiac pumping function, is still a major clinical problem with a high rate of early and long-term mortality. Post-cardiac arrest syndrome (PCAS) may be related to an early systemic inflammatory response leading to exaggerated and sustained neuroinflammation. Therefore, early intervention with targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes. Using a clinically relevant asphyxia CA model, we demonstrate that a single (i.p.) dose of dendrimer-N-acetylcysteine conjugate (D-NAC), can target “activated” microglial cells following CA, leading to an improvement in post-CA survival rate compared to saline (86% vs. 45%). D-NAC treatment also significantly improved gross neurological score within 4 h of treatment (p < 0.05) and continued to show improvement at 48 h (p < 0.05). Specifically, there was a substantial impairment in motor responses after CA, which was subsequently improved with D-NAC treatment (p < 0.05). D-NAC also mitigated hippocampal cell density loss seen post-CA in the CA1 and CA3 subregions (p < 0.001). These results demonstrate that early therapeutic intervention even with a single D-NAC bolus results in a robust sustainable improvement in long-term survival, short-term motor deficits, and neurological recovery. Our current work lays the groundwork for a clinically relevant therapeutic approach to treating post-CA syndrome.

中文翻译:

全身给药树枝状大分子 N-乙酰半胱氨酸可改善心脏骤停后的预后和存活率

心脏骤停(CA),即有效心脏泵血功能的突然停止,仍然是一个主要的临床问题,早期和长期死亡率很高。心脏骤停后综合征 (PCAS) 可能与导致过度和持续的神经炎症的早期全身炎症反应有关。因此,早期干预靶向给药以减轻神经炎症可能会大大改善治疗效果。使用临床相关的窒息 CA 模型,我们证明单剂量 (ip) 的树状大分子-N-乙酰半胱氨酸缀合物 (D-NAC) 可以靶向 CA 后“激活”的小胶质细胞,从而提高 CA 后的存活率与生理盐水相比(86% 对 45%)。D-NAC 治疗还显着改善了治疗后 4 小时内的总神经功能评分(p < 0.05) 并在 48 小时继续显示改善 ( p  < 0.05)。具体而言,CA 后运动反应存在显着损害,随后通过 D-NAC 治疗得到改善(p  < 0.05)。D-NAC 还减轻了 CA1 和 CA3 亚区 CA 后海马细胞密度损失(p  < 0.001)。这些结果表明,即使是单次 D-NAC 推注,早期治疗干预也会导致长期生存、短期运动障碍和神经恢复方面的稳健可持续改善。我们目前的工作为治疗 CA 后综合征的临床相关治疗方法奠定了基础。
更新日期:2021-09-14
down
wechat
bug