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

Aging (Albany NY). 2021 Nov 23;13(22):24815-24828. doi: 10.18632/aging.203717. Epub 2021 Nov 23.

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.

Keywords: CSDH; angiogenic processes; atorvastatin combined with low-dose dexamethasone treatment; inflammatory activities; optimized CSDH rat model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin / pharmacology*
  • Cytokines / metabolism
  • Dexamethasone / pharmacology*
  • Disease Models, Animal
  • Hematoma, Subdural, Chronic / metabolism*
  • Inflammation / metabolism
  • Neovascularization, Physiologic / physiology
  • Rats

Substances

  • Cytokines
  • Dexamethasone
  • Atorvastatin