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.
Highlights
The incidence of chronic subdural hematoma (CSDH) is increasing in the general population, among elderly individuals [1]
Hemorrhage accounts for 0.2–28.6% of hematoma content, suggesting that continuous or intermittent hemorrhage may play an important role in CDSH formation and progression [29]
We found that exosomes can promote angiogenesis with an increased cell permeability and expression of ANG-2, which indicated the newly formed capillaries were immature
Summary
The incidence of chronic subdural hematoma (CSDH) is increasing in the general population, among elderly individuals [1]. It is approximately 1–13/100,000 in the general population [2] and 129.5/100,000 among individuals 80 years of age and older [3]. Given that the number of individuals over 65 years of age will more than triple by 2030, CSDH is projected to become the most common cranial neurosurgical condition in the United States [4]. Most CSDH patients achieve satisfactory outcomes following surgery, the rate of recurrence ranges from 2.5–33% [5]. Longterm outcomes among elderly patients are poor (mortality rates of 26.3% and 32% at 6 months and 1 year postsurgery, respectively) [6]. The major causes of death are disturbance of consciousness at onset and pneumonia [7]
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