Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Prospero Homeobox 1 and Doublecortin Correlate with Neural Damage after Ischemic Stroke

  • Dong-Hun Lee (Department of Neurosurgery Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University) ;
  • Eun Chae Lee (Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea) ;
  • Sang-Won Park (Department of Neurosurgery Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University) ;
  • Ji young Lee (Department of Neurosurgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kee-Pyo Kim (Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea) ;
  • Jae Sang Oh (Department of Neurosurgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2023.07.20
  • Accepted : 2023.10.16
  • Published : 2024.05.01
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Abstract

Objective : Markers of neuroinflammation during ischemic stroke are well characterized, but additional markers of neural damage are lacking. The study identified associations of behavioral disorders after stroke with histologic neural damage and molecular biological change. Methods : Eight-week-old, 25 g male mice of the C57BL/6J strain were subjected to middle cerebral artery occlusion (MCAO) to induce ischemic stroke. The control group was a healthy wild type (WT), and the experimental group were designed as a low severity MCAO1 and a high severity MCAO2 based on post-stroke neurological scoring. All groups underwent behavioral tests, realtime polymerase chain reaction, triphenyltetrazolium chloride (TTC) staining and Hematoxylin and Eosin staining. One-way analysis of variance was used to analyze statistical significance between groups. Results : In TTC staining, MCAO1 showed 29.02% and MCAO2 showed 38.94% infarct volume (p<0.0001). The pro-inflammatory cytokine interleukin (IL)-1β was most highly expressed in MCAO2 (WT 0.44 vs. MCAO1 2.69 vs. MCAO2 5.02, p<0.0001). From the distance to target in the Barnes maze test, WT had a distance of 178 cm, MCAO1 had a distance of 276 cm, and MCAO2 had a distance of 1051 (p=0.0015). The latency to target was 13.3 seconds for WT, 27.9 seconds for MCAO1, and 87.9 seconds for MCAO2 (p=0.0007). Prospero homeobox 1 (Prox1) was most highly expressed in MCAO2 (p=0.0004). Doublecortin (Dcx) was most highly expressed in MCAO2 (p<0.0001). Conclusion : The study demonstrated that histological damage to neural cells and changes in brain mRNA expression were associated with behavioral impairment after ischemic stroke. Prox1 and Dcx may be biomarkers of neural damage associated with long-term cognitive decline, and increased expression at the mRNA level was consistent with neural damage and long-term cognitive dysfunction.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government (2023RA1A2C100531), by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (HC22C0043). The author(s) wish(es) to ac - knowledge the f inancial support of The Catholic University of Korea Uijeongbu St. Mary's Hospital Clinical Research Laboratory Foundation made in the program year of 2023.

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