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Fraxinellone ameliorates intracerebral hemorrhage-induced secondary brain injury by regulating Krüppel-like transcription factor 2 expression in rats.

Abstract
Damage to the blood-brain barrier (BBB) is an important factor leading to intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Krüppel-like transcription factor 2 (KLF2) plays an important role in the maintenance of the BBB. This study aims to detect the changes of KLF2 after ICH and evaluate the potential effects of fraxinellone on ICH-induced SBI and its correlation with KLF2. An ICH model was established by injecting autologous blood into the right basal ganglia of Sprague-Dawley (SD) rats. First, after ICH induction, the protein levels of KLF2 were reduced. Then, we found that the decrease of KLF2 protein levels induced by ICH could be effectively reversed with the treatment of fraxinellone in vascular endothelial cells. Furthermore, fraxinellone treatment effectively alleviated brain edema, decreased the levels of TNF-α and IL-1β, and improved neuronal cell degeneration induced by ICH. Meanwhile, fraxinellone ameliorated neurobehavioral disorders, motor and sensory impairments, and neurobehavioral disorders and memory loss caused by ICH. Collectively, these findings reveal that KLF2 may be a potential target for fraxinellone to exert neuroprotective effects after ICH, and fraxinellone could be a potential therapeutic agent for SBI after ICH.
AuthorsTing Lu, Songyang Peng, Jiahe Wang, Siyuan Yang, Xiang Xu, Haiying Li, Haitao Shen, Xiang Li, Gang Cui, Gang Chen
JournalBrain research bulletin (Brain Res Bull) Vol. 177 Pg. 340-351 (12 2021) ISSN: 1873-2747 [Electronic] United States
PMID34717966 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 Elsevier Inc. All rights reserved.
Chemical References
  • Benzofurans
  • Klf2 protein, rat
  • Kruppel-Like Transcription Factors
  • fraxinellone
Topics
  • Animals
  • Benzofurans
  • Brain Edema (drug therapy, etiology)
  • Brain Injuries (metabolism)
  • Cerebral Hemorrhage (complications, drug therapy, metabolism)
  • Disease Models, Animal
  • Endothelial Cells (metabolism)
  • Kruppel-Like Transcription Factors (therapeutic use)
  • Rats
  • Rats, Sprague-Dawley

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