Pomalidomide Reduces Ischemic Brain Injury in Rodents

Yan Rou Tsai, David Tweedie, Ignacio Navas-Enamorado, Michael T. Scerba, Cheng Fu Chang, Jing Huei Lai, John Chung Che Wu, Yen Hua Chen, Shuo Jhen Kang, Barry J. Hoffer, Rafael de Cabo, Nigel H. Greig, Yung Hsiao Chiang, Kai Yun Chen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)439-450
Number of pages12
JournalCell Transplantation
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

Fingerprint

Brain Injuries
Rodentia
Brain
Rats
Surface active agents
Brain Ischemia
Proteins
Oxygen
Oxidative stress
Pharmacokinetics
Middle Cerebral Artery Infarction
Protein C
Surface-Active Agents
Enzymes
Chemical activation
Reactive Oxygen Species
Tissue
Stroke
Plasmas
Inflammation

Keywords

  • cerebral ischemia
  • pomalidomide
  • pulmonary fibrosis
  • stroke
  • thalidomide
  • TNF-α

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Tsai, Y. R., Tweedie, D., Navas-Enamorado, I., Scerba, M. T., Chang, C. F., Lai, J. H., ... Chen, K. Y. (2019). Pomalidomide Reduces Ischemic Brain Injury in Rodents. Cell Transplantation, 28(4), 439-450. https://doi.org/10.1177/0963689719850078

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.

In: Cell Transplantation, Vol. 28, No. 4, 01.04.2019, p. 439-450.

Research output: Contribution to journalArticle

Tsai, YR, Tweedie, D, Navas-Enamorado, I, Scerba, MT, Chang, CF, Lai, JH, Wu, JCC, Chen, YH, Kang, SJ, Hoffer, BJ, de Cabo, R, Greig, NH, Chiang, YH & Chen, KY 2019, 'Pomalidomide Reduces Ischemic Brain Injury in Rodents', Cell Transplantation, vol. 28, no. 4, pp. 439-450. https://doi.org/10.1177/0963689719850078
Tsai YR, Tweedie D, Navas-Enamorado I, Scerba MT, Chang CF, Lai JH et al. Pomalidomide Reduces Ischemic Brain Injury in Rodents. Cell Transplantation. 2019 Apr 1;28(4):439-450. https://doi.org/10.1177/0963689719850078
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. / Pomalidomide Reduces Ischemic Brain Injury in Rodents. In: Cell Transplantation. 2019 ; Vol. 28, No. 4. pp. 439-450.
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