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止血纳米颗粒可提高创伤性爆炸伤模型中小鼠的存活率,减轻神经病理学损伤并缓解焦虑。

Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model.

机构信息

Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, USA.

Spinal Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky College of Medicine, Lexington, KY, USA.

出版信息

Sci Rep. 2018 Jul 13;8(1):10622. doi: 10.1038/s41598-018-28848-2.

Abstract

Explosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.

摘要

爆炸占战斗相关伤害的 79%,并且经常导致多发伤,其中大多数包括爆炸引起的创伤性脑损伤 (bTBI)。这些损伤会导致多个器官内出血,而在 bTBI 的情况下,会导致长期的神经功能缺陷。目前,除了液体复苏和手术之外,没有针对内出血的治疗方法。TBI 的治疗方法也很少。我们开发了一种使用止血纳米粒子的新方法,这些纳米粒子封装了一种抗炎药地塞米松,以在受伤后止血并减少炎症。我们假设这不仅可以提高生存率,还可以改善爆炸多发伤后的长期功能结果。制备并测试了包封地塞米松的聚(乳酸-共-乙醇酸)止血纳米粒子(hDNPs),并与适当的对照一起进行了损伤后的测试。使用先进的爆炸模拟器使大鼠暴露于单次爆炸波,引起原发性爆炸肺和 bTBI。与对照组相比,hDNPs 组的存活率提高。与 hDNPs 相比,对照组的焦虑参数升高。组织学分析表明,与 hDNPs 和假手术组相比,对照组杏仁核中的细胞凋亡和血脑屏障破坏明显增加。立即干预对于减轻导致情绪缺陷的损伤机制至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a23/6045585/130e19cb9a8e/41598_2018_28848_Fig1_HTML.jpg

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