摘要
原文 | 英語 |
---|---|
頁(從 - 到) | 439-450 |
頁數 | 12 |
期刊 | Cell Transplantation |
卷 | 28 |
發行號 | 4 |
DOIs | |
出版狀態 | 已發佈 - 四月 1 2019 |
指紋
ASJC Scopus subject areas
- Biomedical Engineering
- Cell Biology
- Transplantation
引用此文
Pomalidomide Reduces Ischemic Brain Injury in Rodents. / Tsai, Yan Rou; Tweedie, David; Navas-Enamorado, Ignacio; Scerba, Michael T.; Chang, Cheng Fu; Lai, Jing Huei; Wu, John Chung Che; Chen, Yen Hua; Kang, Shuo Jhen; Hoffer, Barry J.; de Cabo, Rafael; Greig, Nigel H.; Chiang, Yung Hsiao; Chen, Kai Yun.
於: Cell Transplantation, 卷 28, 編號 4, 01.04.2019, p. 439-450.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Pomalidomide Reduces Ischemic Brain Injury in Rodents
AU - Tsai, Yan Rou
AU - Tweedie, David
AU - Navas-Enamorado, Ignacio
AU - Scerba, Michael T.
AU - Chang, Cheng Fu
AU - Lai, Jing Huei
AU - Wu, John Chung Che
AU - Chen, Yen Hua
AU - Kang, Shuo Jhen
AU - Hoffer, Barry J.
AU - de Cabo, Rafael
AU - Greig, Nigel H.
AU - Chiang, Yung Hsiao
AU - Chen, Kai Yun
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Stroke is a leading cause of death and severe disability worldwide. After cerebral ischemia, inflammation plays a central role in the development of permanent neurological damage. Reactive oxygen species (ROS) are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Prior cellular studies demonstrate that POM can mitigate oxidative stress and lower levels of pro-inflammatory cytokines, particularly TNF-α, which plays a prominent role in ischemic stroke-induced brain damage and functional deficits. To evaluate the potential value of POM in cerebral ischemia, POM was initially administered to transgenic mice chronically over-expressing TNF-α surfactant protein (SP)-C promoter (SP-C/TNF-α mice) to assess whether systemically administered drug could lower systemic TNF-α level. POM significantly lowered serum levels of TNF-α and IL-5. Pharmacokinetic studies were then undertaken in mice to evaluate brain POM levels following systemic drug administration. POM possessed a brain/plasma concentration ratio of 0.71. Finally, rats were subjected to transient middle cerebral artery occlusion (MCAo) for 60 min, and subsequently treated with POM 30 min thereafter to evaluate action on cerebral ischemia. POM reduced the cerebral infarct volume in MCAo-challenged rats and improved motor activity, as evaluated by the elevated body swing test. POM’s neuroprotective actions on ischemic injury represent a potential therapeutic approach for ischemic brain damage and related disorders, and warrant further evaluation.
AB - Stroke is a leading cause of death and severe disability worldwide. After cerebral ischemia, inflammation plays a central role in the development of permanent neurological damage. Reactive oxygen species (ROS) are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Prior cellular studies demonstrate that POM can mitigate oxidative stress and lower levels of pro-inflammatory cytokines, particularly TNF-α, which plays a prominent role in ischemic stroke-induced brain damage and functional deficits. To evaluate the potential value of POM in cerebral ischemia, POM was initially administered to transgenic mice chronically over-expressing TNF-α surfactant protein (SP)-C promoter (SP-C/TNF-α mice) to assess whether systemically administered drug could lower systemic TNF-α level. POM significantly lowered serum levels of TNF-α and IL-5. Pharmacokinetic studies were then undertaken in mice to evaluate brain POM levels following systemic drug administration. POM possessed a brain/plasma concentration ratio of 0.71. Finally, rats were subjected to transient middle cerebral artery occlusion (MCAo) for 60 min, and subsequently treated with POM 30 min thereafter to evaluate action on cerebral ischemia. POM reduced the cerebral infarct volume in MCAo-challenged rats and improved motor activity, as evaluated by the elevated body swing test. POM’s neuroprotective actions on ischemic injury represent a potential therapeutic approach for ischemic brain damage and related disorders, and warrant further evaluation.
KW - cerebral ischemia
KW - pomalidomide
KW - pulmonary fibrosis
KW - stroke
KW - thalidomide
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=85068930694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068930694&partnerID=8YFLogxK
U2 - 10.1177/0963689719850078
DO - 10.1177/0963689719850078
M3 - Article
C2 - 31094216
AN - SCOPUS:85068930694
VL - 28
SP - 439
EP - 450
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 4
ER -