Research Paper Volume 13, Issue 22 pp 24815—24828

Atorvastatin combined with dexamethasone promote hematoma absorption in an optimized rat model of chronic subdural hematoma

Dong Wang1,2, *, , Yueshan Fan1,2,3, *, , Jun Ma1,2, *, , Chuang Gao1,2, , Xuanhui Liu1,2,3, , Zilong Zhao1,2, , Huijie Wei1,2, , Guili Yang1,2, , Jinhao Huang1,2, , Rongcai Jiang1,2, , Jianning Zhang1,2, ,

  • 1 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, Tianjin, China
  • 2 Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, Tianjin, China
  • 3 Tianjin Medical University, Tianjin 300070, Tianjin, China
* Equal contribution

Received: July 5, 2021       Accepted: October 26, 2021       Published: November 23, 2021      

https://doi.org/10.18632/aging.203717
How to Cite

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Previous studies found that atorvastatin and dexamethasone were effective in promoting the absorption of chronic subdural hematoma. In this study, we aimed to investigate the effect of pharmacotherapy in an optimized rat model of chronic subdural hematoma.

Rat model of chronic subdural hematoma via a bEnd.3 cell and Matrigel mix was established and dynamic changes in different drug treatment groups were tested. The hematoma gradually increased, peaked on the fifth day (263.8±52.85 μl), and was completely absorbed in two weeks. Notably, Kruppelle-like factor 2 expression was significantly decreased with increasing hematoma volume, and then increased in the repair period. The expression of IL-10 was increased and peaked on 7 days, and then decreased at 14 days. The dynamic trends of IL-6, IL-8, MMP-9, and VEGF were also increased first and then decreased. Both monotherapy and the combined treatment by atorvastatin and dexamethasone could counteract the inflammatory activities, decrease hematoma permeability, and improve hematoma absorption, however, most prominent in combined group. The combined treatment could more effectively increase Kruppelle-like factor 2 and ZO-1 expression, attenuate the expression of NF-κb. Most importantly, the combined treatment enhanced the neural functional prognosis and reduced the mortality of chronic subdural hematoma rats.

According to our results, the combined treatment could more effectively attenuate inflammatory. And it could also enhance angiogenic activities which could promote the stability of local function and structure of the hematoma cavity, reduce the hematoma volume and improve the outcomes of rats with chronic subdural hematoma than single treatments in the optimized chronic subdural hematoma model.

Abbreviations

CSDH: chronic subdural hematoma; KLF-2: Kruppelle-like factor 2; SDH: subdural hematoma; SD: Sprague Dawley; DMEM: Dulbecco’s Modified Eagle’s Medium; ATCC: American Type Culture Collection; PBS: phosphate buffer saline; MRI: magnetic resonance imaging; GRE: gradient echo; ELISA: enzyme-linked immunosorbent assays; qRT-PCR: quantitative real-time polymerase chain reaction; ANOVA: one-way analysis of variance.