Dataset Information

Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p.

ABSTRACT: Exosomes are small (30-150 nm diameter) lipid bilayer-enclosed vesicles found in all bodily fluids. We investigated whether exosomes play a role in chronic subdural hematoma (CSDH). Exosomes were identified and characterized using transmission electron microscopy and NanoSight particle tracking. The functions of hematoma-derived exosomes were evaluated in a rat model of acute subdural hematoma (SDH). The hematoma-derived exosomes inhibited hematoma absorption and exacerbated neurological deficits in SDH rats. We examined the effects of the exosomes on angiogenesis and cell permeability in human umbilical vein endothelial cells (HUVECs). Co-culture of exosomes with HUVECs revealed that the hematoma-derived exosomes were taken-in by the HUVECs, resulting in enhanced tube formation and vascular permeability. Additionally, there was a concomitant increase in ANG-2 expression and decrease in ANG-1 expression. Exosomes were enriched with microRNAs including miR-144-5p, which they could deliver to HUVECs to promote angiogenesis and increase membrane permeability. Overexpression of miR-144-5p in HUVECs and in SDH rats promoted abnormal angiogenesis and reduced hematoma absorption, which mimicked the effects of the hematoma-derived exosomes both in vitro and in vivo. Thus, hematoma-derived exosomes promote abnormal angiogenesis with high permeability and inhibit hematoma absorption through miR-144-5p in CSDH.

SUBMITTER: Gao C

PROVIDER: S-EPMC6949077 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p.

Gao Chuang C Gong Zhitao Z Wang Dong D Huang Jinhao J Qian Yu Y Nie Meng M Jiang Weiwei W Liu Xuanhui X Luo Hongliang H Yuan Jiangyuan J Xiang Tangtang T An Shuo S Quan Wei W Wei Huijie H Zhang Jianning J Jiang Rongcai R

Aging 20191216 24

Exosomes are small (30-150 nm diameter) lipid bilayer-enclosed vesicles found in all bodily fluids. We investigated whether exosomes play a role in chronic subdural hematoma (CSDH). Exosomes were identified and characterized using transmission electron microscopy and NanoSight particle tracking. The functions of hematoma-derived exosomes were evaluated in a rat model of acute subdural hematoma (SDH). The hematoma-derived exosomes inhibited hematoma absorption and exacerbated neurological deficit ...[more]

PMID: 31841443

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Project description:Background: Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness of different classes of medication. We performed a Bayesian network meta-analysis to compare and rank the efficacy and safety of five drug regimens to determine the best treatment for this group of patients. Methods: We systematically searched PubMed, Medline, clinicaltrials.gov, the Cochrane database, and Embase to identify relevant randomized clinical trials (RCTs) comparing drug treatments in adult patients with CSDH. A network meta-analysis was conducted using a Bayesian framework. Random- and fixed-effects models were used to pool the network results, and the preferred model was selected by comparing the deviance information criteria (DIC). Efficacy outcomes included recurrence requiring surgery, changes in hematoma volume, and a good recovery. The safety outcomes were treatment-related adverse events and all-cause mortality. Results: In this Bayesian network meta-analysis, available data were obtained from 12 eligible trials, including 2,098 patients and 5 techniques. Compared to placebo, atorvastatin (RR: 0.45, 95% CrI: 0.24-0.81) and dexamethasone (RR: 0.38, 95% CrI: 0.22-0.63) were similarly effective in reducing recurrence requiring surgery by 55% and 62%, respectively. Dexamethasone (RR: 0.46, 95% CrI: 0.23-0.91) was more effective in reducing recurrence requiring surgery than goreisan. Additionally, atorvastatin reduced the hematoma volume to a greater extent than placebo (MD: -7.44, 95% CrI: -9.49 to -5.43) or goreisan (MD: -14.09, 95% CrI: -23.35 to -4.82). Moreover, tranexamic acid (MD: -12.07, 95% CrI: -21.68 to -2.29) reduced the hematoma volume to a greater extent than goreisan. No significant differences were detected between drugs and placebo with regard to a good recovery. In terms of safety, dexamethasone (RR: 1.96, 95% CrI: 1.20-3.28) increased the risk of mortality compared to placebo. Conclusion: These findings suggest that dexamethasone is the best treatment to reduce recurrence and atorvastatin is the best treatment to reduce hematoma volume in patients with CSDH. However, clinicians should pay close attention to the elevated risk of all-cause mortality and potential adverse events caused by dexamethasone. Future well-designed RCTs with more participants are needed to verify these findings. Clinical Trial Registration: http://osf.io/u9hqp.

Project description:BackgroundBurr hole evacuation is a well-established treatment for symptomatic cases with chronic subdural hematoma (cSDH). Routinely postoperative catheter is left in the subdural space to drain the residual blood. Drainage obstruction is commonly seen, and it can be related to suboptimal treatment.MethodsTwo groups of patients submitted to cSDH surgery were evaluated in a retrospective non-randomized trial, one group that had conventional subdural drainage (CD group, n = 20) and another group that used an anti-thrombotic catheter (AT group, n = 14). We compared the obstruction rate, amount of drainage and complications. Statistical analyses were done using SPSS (v.28.0).ResultsFor AT and CD groups respectively (median ± IQR), the age was 68.23 ± 26.0 and 70.94 ± 21.5 (p > 0.05); preoperative hematoma width was 18.3 ± 11.0 mm and 20.7 ± 11.7 mm and midline shift was 13.0 ± 9.2 and 5.2 ± 8.0 mm (p = 0.49). Postoperative hematoma width was 12.7 ± 9.2 mm and 10.8 ± 9.0 mm (p < 0.001 intra-groups compared to preoperative) and MLS was 5.2 ± 8.0 mm and 1.5 ± 4.3 mm (p < 0.05 intra-groups). There were no complications related to the procedure including infection, bleed worsening and edema. No proximal obstruction was observed on the AT, but 8/20 (40%) presented proximal obstruction on the CD group (p = 0.006). Daily drainage rates and length of drainage were higher in AT compared to CD: 4.0 ± 1.25 days vs. 3.0 ± 1.0 days (p < 0.001) and 69.86 ± 106.54 vs. 35.00 ± 59.67 mL/day (p = 0.074). Symptomatic recurrence demanding surgery occurred in two patients of CD group (10%) and none in AT group (p = 0.230), after adjusting for MMA embolization, there was still no difference between groups (p = 0.121).ConclusionThe anti-thrombotic catheter for cSDH drainage presented significant less proximal obstruction than the conventional one and higher daily drainage rates. Both methods demonstrated to safe and effective for draining cSDH.

Dataset Information

Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p.

Publications

Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p.

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