Endocrine Regulator rFGF21 (Recombinant Human Fibroblast Growth Factor 21) Improves Neurological Outcomes Following Focal Ischemic Stroke of Type 2 Diabetes Mellitus Male Mice

doi:10.1161/STROKEAHA.118.022119

科研成果详情

题名	Endocrine Regulator rFGF21 (Recombinant Human Fibroblast Growth Factor 21) Improves Neurological Outcomes Following Focal Ischemic Stroke of Type 2 Diabetes Mellitus Male Mice
作者	Jiang, Yinghua 1,2; Liu, Ning 2,3; Wang, Qingzhi 2,4; Yu, Zhanyang 2,4; Lin, Li2,5; Yuan, Jing 2; Guo, Shuzhen 2; Ahn, Bum Ju 2; Wang, Xiao-Jie 5; Li, Xiaokun5; Lo, Eng H.2; Sun, Xiaochuan 1; Wang, Xiaoying 2
发表日期	2018-12
发表期刊	STROKE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	diabetes mellitus inflammation mice stroke white matter
其他关键词	VASCULAR-DISEASE PATHOPHYSIOLOGY ; CLINICAL CONSEQUENCES ; FUNCTIONAL RECOVERY ; BRAIN-DAMAGE ; FGF21 ; INJURY
摘要	Background and Purpose-The complexity and heterogeneity of stroke, as well as the associated comorbidities, may render neuroprotective drugs less efficacious in clinical practice. Therefore, the development of targeted therapies to specific patient subsets has become a high priority in translational stroke research. Ischemic stroke with type 2 diabetes mellitus has a nearly double mortality rate and worse neurological outcomes. In the present study, we tested our hypothesis that rFGF21 (recombinant human fibroblast growth factor 21) administration is beneficial for improving neurological outcomes of ischemic stroke with type 2 diabetes mellitus. Methods-Type 2 diabetes mellitus db/db and nondiabetic genetic control db/+ mice were subjected into permanent focal ischemia of distal middle cerebral artery occlusion, we examined the effects of poststroke administration with rFGF21 in systemic metabolic disorders, inflammatory gatekeeper PPAR. (peroxisome proliferator-activated receptor.) activity at 3 days, mRNA expression of inflammatory cytokines and microglia/macrophage activation at 7 days in the perilesion cortex, and last neurological function deficits, ischemic brain infarction, and white matter integrity up to 14 days after stroke of db/db mice. Results-After permanent focal ischemia, diabetic db/db mice presented confounding pathological features, including metabolic dysregulation, more severe brain damage, and neurological impairment, especially aggravated proinflammatory response and white matter integrity loss. However, daily rFGF21 treatment initiated at 6 hours after stroke for 14 days significantly normalized systemic metabolic disorders, rescued PPAR. activity decline, inhibited proinflammatory cytokine mRNA expression, and M1-like microglia/macrophage activation in the brain. Importantly, rFGF21 also significantly reduced white matter integrity loss, ischemic brain infarction, and neurological function deficits up to 14 days after stroke. The potential mechanisms of rFGF21 may in part consist of potent systematic metabolic regulation and PPAR.-activation promotion-associated antiproinflammatory roles in the brain. Conclusions-Taken together, these results suggest rFGF21 might be a novel and potent candidate of the disease-modifying strategy for treating ischemic stroke with type 2 diabetes mellitus. Visual Overview-An online visual overview is available for this article.
资助项目	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RO1 NS099539]; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS099539] Funding Source: NIH RePORTER
出版者	LIPPINCOTT WILLIAMS & WILKINS
出版地	PHILADELPHIA
ISSN	0039-2499
EISSN	1524-4628
卷号	49 期号:12 页码:3039-3049
DOI	10.1161/STROKEAHA.118.022119
页数	11
WOS类目	Clinical Neurology ; Peripheral Vascular Disease
WOS研究方向	Neurosciences & Neurology ; Cardiovascular System & Cardiology
WOS记录号	WOS:000456427700046
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	30571410
PMC记录号	PMC6310061
SCOPUSEID	2-s2.0-85058925883
通讯作者地址	[Sun, Xiaochuan]Department of Neurosurgery,First Affiliated Hospital of Chongqing Medical University,No. 1 Youyi Road,Yuzhong District, Chongqing,400016,China
Scopus学科分类	Neurology (clinical);Cardiology and Cardiovascular Medicine;Advanced and Specialized Nursing
TOP期刊	TOP期刊
引用统计	被引频次：15[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/19660
专题	药学院（分析测试中心）_生物制药系_生物制药工程
通讯作者	Sun, Xiaochuan
作者单位	1.Department of Neurosurgery,First Affiliated Hospital of Chongqing Medical University,No. 1 Youyi Road,Yuzhong District, Chongqing,400016,China; 2.Neuroprotection Research Laboratory,Departments of Radiology and Neurology,Massachusetts General Hospital,Harvard Medical School,149 13th St,Charlestown,02129,United States; 3.Third Affiliated Hospital of Zhengzhou University,China; 4.Department of Neurology,First Affiliated Hospital of Zhengzhou University,China; 5.Key Laboratory of Biotechnology and Pharmaceutical Engineering,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,China
推荐引用方式 GB/T 7714	Jiang, Yinghua,Liu, Ning,Wang, Qingzhi,et al. Endocrine Regulator rFGF21 (Recombinant Human Fibroblast Growth Factor 21) Improves Neurological Outcomes Following Focal Ischemic Stroke of Type 2 Diabetes Mellitus Male Mice[J]. STROKE,2018,49(12):3039-3049.
APA	Jiang, Yinghua., Liu, Ning., Wang, Qingzhi., Yu, Zhanyang., Lin, Li., ... & Wang, Xiaoying. (2018). Endocrine Regulator rFGF21 (Recombinant Human Fibroblast Growth Factor 21) Improves Neurological Outcomes Following Focal Ischemic Stroke of Type 2 Diabetes Mellitus Male Mice. STROKE, 49(12), 3039-3049.
MLA	Jiang, Yinghua,et al."Endocrine Regulator rFGF21 (Recombinant Human Fibroblast Growth Factor 21) Improves Neurological Outcomes Following Focal Ischemic Stroke of Type 2 Diabetes Mellitus Male Mice".STROKE 49.12(2018):3039-3049.