2. Academic Validation
  3. Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation

Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation

  • Inflammation. 2024 Aug 9. doi: 10.1007/s10753-024-02082-7.
Shenglong Mo # 1 2 3,  Chengmin Yang # 1 2,  Xingwu Zheng # 4,  Hui Lv # 5,  Sanyin Mao 6,  Ning Liu 7,  Qin Yang 8,  Bao Liao 8,  Meiling Yang 3,  Zhicheng Lu 3,  Lina Tang 3,  Xiaorui Huang 9,  Chongdong Jian 10 11,  Xuebin Li 12 13,  Jingwei Shang 14 15
Affiliations

Affiliations

  • 1 Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
  • 2 Biological Molecule Laboratory, Guangxi University Key Laboratory of High Incidence Prevention and Control Research in Western Guangxi, Baise, 53300, Guangxi, China.
  • 3 Graduate School of Youjiang, Medical University for Nationalities, Baise, Guangxi, China.
  • 4 Department of Geriatrics, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
  • 5 Modern Industrial College of Biomedicine and Great Health, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
  • 6 Department of Neurology, The First People's Hospital of Jiande, Hangzhou, China.
  • 7 School of Basic Medical Sciences, Beihua University, Jilin, China.
  • 8 Department of Neurology, BAISE PEOPLE'S HOSPITAL, Baise, Guangxi, China.
  • 9 Department of Psychiatry and Psychology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
  • 10 Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China. jianchongdong@163.com.
  • 11 Biological Molecule Laboratory, Guangxi University Key Laboratory of High Incidence Prevention and Control Research in Western Guangxi, Baise, 53300, Guangxi, China. jianchongdong@163.com.
  • 12 Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China. 13507766338@139.com.
  • 13 Biological Molecule Laboratory, Guangxi University Key Laboratory of High Incidence Prevention and Control Research in Western Guangxi, Baise, 53300, Guangxi, China. 13507766338@139.com.
  • 14 Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China. shangjw1979@yahoo.co.jp.
  • 15 Biological Molecule Laboratory, Guangxi University Key Laboratory of High Incidence Prevention and Control Research in Western Guangxi, Baise, 53300, Guangxi, China. shangjw1979@yahoo.co.jp.
  • # Contributed equally.
PMID: 39117789 DOI: 10.1007/s10753-024-02082-7
Abstract

Following ischemic stroke, Aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and Caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating Apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.

Keywords

AER-271; AQP4; apoptosis; autophagy; inflammation.

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