Abstract WP340: Dimethyl Fumarate Controls Inflammation-Associated Brain Damage under Hypoxia through Nrf2 Mechanism

神经保护 炎症 胶质增生 医学 小胶质细胞 缺血 缺氧(环境) 发病机制 药理学 神经炎症 脑损伤 免疫学 病理 内科学 化学 氧气 有机化学
作者
Tyler G. Fernandez,Lei Liu,Mary K. Vollmer,Victoria M. Fernandez,Hocheol Kim,Sylvain Doré
出处
期刊:Stroke [Lippincott Williams & Wilkins]
卷期号:50 (Suppl_1) 被引量:1
标识
DOI:10.1161/str.50.suppl_1.wp340
摘要

Introduction: Cerebral ischemia triggers a complex cascade of pathophysiological changes including the activation of resident cells, production of inflammatory mediators and infiltration of inflammatory cells. Clinical and experimental studies have revealed that inflammatory interaction following cerebral ischemia is closely related to the pathogenesis and the extent of ischemic brain injury. Therefore, targeting inflammation modulation has emerged as a promising therapeutic strategy. Dimethyl fumarate (DMF) is a typical transcriptional factor Nrf2 activator that exhibits an encouraging anti-inflammatory property. However, the effect of DMF on inflammation-associated ischemic brain injury is still inconclusive. Hypothesis: Here, we present that Nrf2 can serve as a modulator that links inflammation and subsequent brain injury following ischemia. Methods: Adult Nrf2 knockout and WT mice were pretreated with DMF for 7 days and were subjected to cerebral hypoxia-ischemia (HI) surgery. The infarct volume, neurobiological deficits, reactive gliosis, inflammatory mediators, and Nrf2 target protein were examined after HI. Results: DMF significantly reduced the ischemia-induced infarct volume, brain edema (P≤0.05, n=4-6) and neurological deficits (P≤0.05, n=7-11) in WT, but not Nrf2 -/- , mice at both 6h and 24h after HI. In both ischemic striatum and cortex, the inflammation associated reactive gliosis in astrocyte and microglia at a spatiotemporal pattern was significantly attenuated by DMF in ischemic-WT mice (P≤0.05, n=4-6), correlating well with the Nrf2-dependent neuroprotection by DMF. Meanwhile, DMF dramatically suppressed the expression levels of pro-inflammatory mediators and enhanced the expression levels of Nrf2 downstream cytoprotective proteins (P≤0.05, n=4-5), thereby supporting the Nrf2-mediated neuroprotection by DMF in this process. Conclusion: Overall, this proof-of-principle study provided the direct in vivo evidence that Nrf2 activation by DMF suppresses the neuro-inflammation and leads to long-last neuroprotection against ischemic brain damage.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
高中生完成签到,获得积分10
刚刚
ChrisKim发布了新的文献求助10
刚刚
博士发布了新的文献求助10
刚刚
1秒前
ttttsy完成签到 ,获得积分10
1秒前
1秒前
1秒前
2秒前
3秒前
朱文琛完成签到,获得积分10
4秒前
tuanzi完成签到 ,获得积分20
4秒前
伶俐绮发布了新的文献求助10
4秒前
Ruby发布了新的文献求助10
4秒前
5秒前
5秒前
SciGPT应助小麻花采纳,获得30
5秒前
5秒前
ZZC发布了新的文献求助30
5秒前
依依完成签到 ,获得积分10
6秒前
xiutang完成签到 ,获得积分10
7秒前
韩涵发布了新的文献求助10
7秒前
香菜大王发布了新的文献求助10
7秒前
niuzai完成签到,获得积分10
8秒前
英姑应助研友_8RyzBZ采纳,获得10
8秒前
Jocelyn7完成签到,获得积分10
8秒前
8秒前
jackten完成签到,获得积分10
8秒前
9秒前
9秒前
Tangyartie发布了新的文献求助10
9秒前
漂风完成签到 ,获得积分10
10秒前
学术悍匪完成签到,获得积分10
10秒前
周一完成签到,获得积分10
10秒前
10秒前
松鼠桂鱼发布了新的文献求助10
11秒前
xrL发布了新的文献求助10
13秒前
学术悍匪发布了新的文献求助10
14秒前
希望天下0贩的0应助艺玲采纳,获得10
15秒前
斯文败类应助伶俐绮采纳,获得10
16秒前
澡雪发布了新的文献求助10
16秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Effective Learning and Mental Wellbeing 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3976058
求助须知:如何正确求助?哪些是违规求助? 3520294
关于积分的说明 11202245
捐赠科研通 3256804
什么是DOI,文献DOI怎么找? 1798471
邀请新用户注册赠送积分活动 877610
科研通“疑难数据库(出版商)”最低求助积分说明 806496