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Background <p>Chronic cerebral hypoperfusion (CCH) is a critical pathophysiological mechanism underlying cerebral small vessel disease (CSVD). Accumulating evidence have demonstrated that resident pericytes and deposit extracellular matrix (ECM) and play a key role in mediating fibrosis in hypoxic changes. Edaravone dexborneol (EDB) is known to target multiple pathways involved in fibrosis.</p> Methods <p>We constructed the CCH mouse models that were subjected to either PBS or EDB at different concentrations. Measures of cognitive function, neuronal damage, white matter lesion (WML), the fibrous profiles of pericytes and ECM protein were investigated to assess the effect of EDB. RNA sequencing of OGD in pericytes was performed to identify a key signaling pathway.</p> Results <p>We observed that both medium and high concentrations of EDB could ameliorate CCH-induced cognitive impairment and emotional disorders. Neuronal damage in cortical layer and hippocampus and WML in corpus callosum were improved by EDB, which was consistent with the tends of fibrous pericytes and ECM proteins in these regions. RNA sequencing suggested that TGF-β1/IL-11 plays an important role in mechanism of pericytes fibrosis. Subsequently, the results of sequencing were confirmed in both cellular and mouse model.</p> Conclusions <p>Our findings reveal the role of pericyte-mediated fibrosis in depositing ECM in the pathogenesis of CSVD. EDB could improve symptoms and the underlying pathogenesis of CCH mice and decrease the expression of the fibrous profiles of pericytes and ECM proteins, which may be regulated by TGF-β1/ IL-11. EDB treatment, targeting pericytes fibrosis, may be a novel therapeutic strategy for CSVD.</p>

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Edaravone dexborneol alleviates pericyte-mediated fibrosis depositing extracellular matrix through TGF-β1/IL-11 in cerebral small vessel disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月5日

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  • Qingrui Duan,
  • Zhiyang Liu,
  • Yuxuan Xing,
  • Haifeng Huang,
  • Lin Zhu,
  • Jiaxuan Liu,
  • Peikun He,
  • Guixian Ma,
  • Yuhu Zhang,
  • Kun Nie,
  • Yuyuan Gao,
  • Lijuan Wang

摘要

Background

Chronic cerebral hypoperfusion (CCH) is a critical pathophysiological mechanism underlying cerebral small vessel disease (CSVD). Accumulating evidence have demonstrated that resident pericytes and deposit extracellular matrix (ECM) and play a key role in mediating fibrosis in hypoxic changes. Edaravone dexborneol (EDB) is known to target multiple pathways involved in fibrosis.

Methods

We constructed the CCH mouse models that were subjected to either PBS or EDB at different concentrations. Measures of cognitive function, neuronal damage, white matter lesion (WML), the fibrous profiles of pericytes and ECM protein were investigated to assess the effect of EDB. RNA sequencing of OGD in pericytes was performed to identify a key signaling pathway.

Results

We observed that both medium and high concentrations of EDB could ameliorate CCH-induced cognitive impairment and emotional disorders. Neuronal damage in cortical layer and hippocampus and WML in corpus callosum were improved by EDB, which was consistent with the tends of fibrous pericytes and ECM proteins in these regions. RNA sequencing suggested that TGF-β1/IL-11 plays an important role in mechanism of pericytes fibrosis. Subsequently, the results of sequencing were confirmed in both cellular and mouse model.

Conclusions

Our findings reveal the role of pericyte-mediated fibrosis in depositing ECM in the pathogenesis of CSVD. EDB could improve symptoms and the underlying pathogenesis of CCH mice and decrease the expression of the fibrous profiles of pericytes and ECM proteins, which may be regulated by TGF-β1/ IL-11. EDB treatment, targeting pericytes fibrosis, may be a novel therapeutic strategy for CSVD.