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

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.

The Effect of Japanese Herbal Medicines (Kampo) Goreisan and Saireito on the Prevention of Recurrent Chronic Subdural Hematoma: A Prospective Randomized Study

“…5 In fact, it has been reported that the administration of statins and steroids reduces the postoperative recurrence rate through anti-inflammatory effects. 9,11,46,47 Because byakujutsu Goreisan has a stronger anti-inflammatory effect than sojutsu Goreisan, [25][26][27] this study may have shown a favorable effect, which was not observed in other prospective randomized studies. Moreover, Saireito has a stronger anti-inflammatory benefit than Goreisan 15,18 because it inhibits proinflammatory cytokines and promotes the endogenous enhancement of steroid secretion through the secretion of hypothalamic corticotropin releasing factor.…”

The Use of Adjuvant Dexamethasone in Chronic Subdural Hematoma After Surgery

“…The concomitant administration of dexamethasone and atorvastatin has been found to be more efficacious in mitigating inflammation and enhancing angiogenic activities. This combined therapy also promotes the stability of the local function and structure of the hematoma cavity, reduces the volume of hematomas, and yields better outcomes in rats with chronic subdural hematomas compared to monotherapy [ 22 ].…”

Dexamethasone for delayed edema after intracerebral hemorrhage： To be or not to be?

“…Some studies have shown that the low expression of KLF2 is closely related to vascular permeability. In vitro studies found that after dexamethasone treatment, mouse endothelial cells showed different levels of high expression of ZO-1 and KLF2, suggesting that dexamethasone can protect the stability of the BBB and reduce exudation [ 9 ]. The NF-κB family consists of five different DNA-binding proteins, which are key regulators of innate and acquired immune responses and play important roles in cell proliferation, inhibition of apoptosis, stimulation of angiogenesis and metastasis.…”