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Aspirin Inhibits Degenerative Changes of Aneurysmal Wall in a Rat Model

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Abstract

Aneurysmal subarachnoid hemorrhage still has a high mortality and morbidity despite notable advances in surgical approaches to cerebral aneurysm (CA). We examined the role of aspirin in vascular inflammation and degeneration. CA was induced in male Sprague–Dawley rats by ligating left common carotid artery and bilateral posterior renal arteries with or without aspirin treatment. The right anterior cerebral artery/olfactory artery (ACA/OA) bifurcations were stripped and assessed morphologically after Verhoeff’s Van Gieson staining. Blood sample was obtained to examine circulating CD34+ CD133+ endothelial progenitor cells (EPCs), platelet aggregation and platelet counts. Macrophages infiltration in aneurysmal wall was evaluated by immunohistochemistry. Expression of matrix metalloproteinase-2 and 9 (MMP-2 and 9), nuclear factor kappa B (NF-κB), macrophage chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) was examined by RT-PCR. 2 months after CA induction, surgically treated rats manifested aneurysmal degeneration in ACA/OA bifurcations. Aspirin-treated rats exhibited a significant decrease in degradation of internal elastic lamina (IEL), medial layer thinning, CA size and macrophages infiltration with reduced expression of MMP-2 and 9 compared with rats in the CA group. RT-PCR demonstrated that the upregulation of NF-κB, MCP-1 and VCAM-1 after CA induction was reversed by aspirin treatment. Aspirin treatment following CA induction increased circulating EPCs to near control levels and reduced platelet aggregation without changing platelet counts. The evidence suggested that aspirin significantly reduced degeneration of aneurysm walls by inhibiting macrophages-mediated chronic inflammation and mobilizing EPCs.

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Abbreviations

CA:

Cerebral aneurysm

EPCs:

Endothelial progenitor cells

PRP:

Platelet-rich plasma

PPP:

Platelet-poor plasma

MNCs:

Mononuclear cells

ACA/OA:

Anterior cerebral artery/olfactory artery

IEL:

Internal elastic lamia

SMCs:

Smooth muscle cells

MMP-2:

Matrix metalloproteinase-2

MMP-9:

Matrix metalloproteinase-9

NF-κB:

Nuclear factor kappa B

MCP-1:

Macrophage chemoattractant protein-1

VCAM-1:

Vascular cell adhesion protein-1

ANOVA:

One-way analysis of variance

ECs:

Endothelial cells

PGE2:

Prostaglandin E2

EP2:

Prostaglandin E receptor 2

ICAM:

Intercellular adhesion molecule

PECAM:

Platelet endothelial cell adhesion molecule

TNF-α:

Tumor necrosis factor-α

ROS:

Reactive oxygen species

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Acknowledgments

The authors acknowledge Weiyun Cui, Fanglian Chen and Lei Zhou for their excellent technical support. This study is supported by the National Natural Science Foundation of China (Grant Nos.: 81100920, 81200907, 81301629 and 81271359), Tianjin Research Program of Application Foundation and Advanced Technology (Grant Nos.: 12JCQNJC6800 and 11JCZDJC18100), Ontario-China Research and Innovation Fund (Grant No.: 2011DFG33430) and Tianjin colleges and universities of science and technology development fund (Grant No.: 2010013).

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China

    Shengjie Li, Dehui Wang, Ye Tian, Huijie Wei, Ziwei Zhou, Li Liu, Dong Wang, Rongcai Jiang & Jianning Zhang

  2. Puget Sound Blood Research Institute, 1551 Eastlake Ave E, Seattle, WA, 98102, USA

    Jing-fei Dong

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  1. Shengjie Li
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Correspondence to Rongcai Jiang or Jianning Zhang.

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Li, S., Wang, D., Tian, Y. et al. Aspirin Inhibits Degenerative Changes of Aneurysmal Wall in a Rat Model. Neurochem Res 40, 1537–1545 (2015). https://doi.org/10.1007/s11064-015-1603-4

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