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在创伤性脑损伤前或损伤后使用胰高血糖素样肽-1受体激动剂艾塞那肽-4进行治疗，可减轻爆炸所致创伤性脑损伤引起的认知缺陷。

Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4.

作者信息

Tweedie David, Rachmany Lital, Rubovitch Vardit, Li Yazhou, Holloway Harold W, Lehrmann Elin, Zhang Yongqing, Becker Kevin G, Perez Evelyn, Hoffer Barry J, Pick Chaim G, Greig Nigel H

机构信息

Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

出版信息

Alzheimers Dement. 2016 Jan;12(1):34-48. doi: 10.1016/j.jalz.2015.07.489. Epub 2015 Aug 29.

DOI:10.1016/j.jalz.2015.07.489
PMID:26327236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4715981/
Abstract

INTRODUCTION

Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently, there are no approved drugs for blast brain injury.

METHODS

Exendin-4 (Ex-4), administered subcutaneously, was evaluated as a pretreatment (48 hours) and postinjury treatment (2 hours) on neurodegeneration, behaviors, and gene expressions in a murine open field model of blast injury.

RESULTS

B-TBI induced neurodegeneration, changes in cognition, and genes expressions linked to dementia disorders. Ex-4, administered preinjury or postinjury, ameliorated B-TBI-induced neurodegeneration at 72 hours, memory deficits from days 7-14, and attenuated genes regulated by blast at day 14 postinjury.

DISCUSSION

The present data suggest shared pathologic processes between concussive and B-TBI, with end points amenable to beneficial therapeutic manipulation by Ex-4. B-TBI-induced dementia-related gene pathways and cognitive deficits in mice somewhat parallel epidemiologic studies of Barnes et al. who identified a greater risk in US military veterans who experienced diverse TBIs, for dementia in later life.

摘要

引言

爆炸所致创伤性脑损伤（B-TBI）影响军事人员和平民。目前，尚无获批用于治疗爆炸脑损伤的药物。

方法

在小鼠爆炸伤开放场模型中，评估皮下注射艾塞那肽-4（Ex-4）作为预处理（48小时）和伤后治疗（2小时）对神经退行性变、行为及基因表达的影响。

结果

B-TBI诱导神经退行性变、认知改变以及与痴呆症相关的基因表达变化。伤前或伤后给予Ex-4，可在72小时改善B-TBI诱导的神经退行性变，在第7至14天改善记忆缺陷，并在伤后第14天减轻爆炸所致的基因调控。

讨论

目前的数据表明，脑震荡和B-TBI之间存在共同的病理过程，其终点可通过Ex-4进行有益的治疗干预。B-TBI诱导的小鼠痴呆相关基因通路和认知缺陷在一定程度上与Barnes等人的流行病学研究结果相似，后者发现经历多种创伤性脑损伤的美国退伍军人晚年患痴呆症的风险更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/11d9cfffd354/nihms714024f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/fa147bd945b0/nihms714024f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/80e215d8fb10/nihms714024f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/7a2f044a7679/nihms714024f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/234722d5b5a4/nihms714024f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/11d9cfffd354/nihms714024f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/fa147bd945b0/nihms714024f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/80e215d8fb10/nihms714024f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/7a2f044a7679/nihms714024f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/234722d5b5a4/nihms714024f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d0/4715981/11d9cfffd354/nihms714024f5.jpg

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Front Neurosci. 2024 Feb 15;18:1342944. doi: 10.3389/fnins.2024.1342944. eCollection 2024.
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