A novel rat model of chronic subdural hematoma: Induction of inflammation and angiogenesis in the subdural space mimicking human-like features of progressively expanding hematoma

Xu, Xin; Wang, Dong; Han, Zhaoxia; Wang, Bo; Gao, Weiwei; Fan, Yueshan; Li, Fanjian; Zhou, Ziwei; Gao, Chuang; Xiong, Jianping; Zhou, Shuai; Zhang, Shu; Yang, Gye Mo; Jiang, Rongcai; Zhang, Jianning

doi:10.1016/j.brainresbull.2021.04.024

Cited by 9 publications

(8 citation statements)

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“…MMPs, along with VEGF, contribute to the instability of newly formed blood vessels, which can lead to a higher risk of hemorrhage [5]. In rats, MMP-9 has been reported to correlate with VEGF concentration in the external neomembrane and promote leaky blood vessel formation and subsequent rebleeding [7]. MMP expression accelerates inflammatory processes by modulating other mediators, such as cytokines and chemokines [5].…”

Section: Discussionmentioning

confidence: 99%

“…In a rat model of CSDH, the profile of inflammatory cytokine expression was elevated in the hematoma membrane and the surrounding tissue [6]. The affected cytokines included pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α); anti-inflammatory cytokines such as interleukin-10 (IL-10) and interleukin-13 (IL-13); and proangiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9) [6,7]. Tsukasa et al suggested that IL-10 acts as a deactivator of inflammation in the pathogenesis of CSDH [8].…”

Section: Introductionmentioning

confidence: 99%

“…However, there is still little evidence regarding the factors influencing CSDH formation in humans [6,7,10]. We aimed to identify one or more factors that may play an important role in the formation of CSDH by examining a series of cytokines in CSDH and in the peripheral serum of affected patients.…”

Section: Introductionmentioning

confidence: 99%

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Serum Levels of MMP-8 and MMP-9 as Markers in Chronic Subdural Hematoma

Gao

et al. 2022

JCM

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Chronic subdural hematoma (CSDH) is a common neurological disease that involves the collection of blood products in the subdural space. The progression of CSDH is an angiogenic and inflammatory process, but the multifactorial mechanisms underlying CSDH are still not fully understood. We aimed to identify one or more factors that may play an important role in the development of CSDH. We enrolled 83 patients with CSDH, including 17 postoperative patients, and analyzed 20 markers in the hematoma fluid and peripheral blood of each patient. Overall differential gene expression was examined to identify the representative markers. The concentration of MMP-8 was significantly lower in the postoperative group than in the preoperative group. The concentration of MMP-9 was significantly higher in the postoperative group than in the preoperative group. These findings indicate that MMP-8 and MMP-9 may play important roles in the pathophysiology of CSDH. Understanding the pathways associated with CSDH may provide insights for improving disease outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum Levels of MMP-8 and MMP-9 as Markers in Chronic Subdural Hematoma

Gao

et al. 2022

JCM

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“…We performed the CSDH model as our previous study [ 10 ]. Matrigel E6909 (Sigma-Aldrich, St. Louis, MO, USA) was placed at 4° C overnight (the colloid liquid state was maintained) before use.…”

Section: Methodsmentioning

confidence: 99%

“…However, these acute blood injection models could partly mimic the process of hematoma injury, but not spontaneous formation or progressive enlargement which is found in the clinical patients. Based on these conditions, we optimized the model with a Matrigel and bEnd.3 cell mixture, which was characterized by spontaneous formation, the formation of a capsule and gradual enlargement of the hematoma [ 10 ]. Following this model, we aimed to further detect the mechanisms of the drug treatment effects on the dynamic changes of the hematoma.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Fan

et al. 2021

Aging

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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.

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