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.
Highlights
Chronic subdural hematoma (CSDH) is a common disease that occurs in elderly individuals
We tested the volume of the hematoma immediately, 3 d, 5 d, 7 d, and 14 d by Magnetic resonance imaging (MRI) spectrometry (GRE) after CSDH injury
At 14 d, most of the hematoma had been absorbed (47.63±21.96 μl, p>0.05). Based on these results we demonstrated that this model successfully mimicked the chronic process of CSDH rather than the acute process
Summary
Chronic subdural hematoma (CSDH) is a common disease that occurs in elderly individuals. In our previous randomized controlled clinical trial, we demonstrated that the application of a low dose and a long course of atorvastatin can accelerate the absorption of CSDH and reduce the rate of operation. A poor effect was observed in 11.2% of the patients (11 operations/98 total) who were only treated with atorvastatin. We applied atorvastatin combined with low-dose dexamethasone to treat patients with CSDH; this combination was much more effective than atorvastatin alone in decreasing the volume of hematoma in preliminary small-scale clinical observation studies [4, 5]. In previous in vitro studies, we found that the combined treatment could counteract hematoma-induced injury in endothelial cells via changing the expression of Kruppelle-like factor 2 (KLF-2) [6, 7]. The mechanism of the combined treatment in vivo remains unclear and requires further study
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