Role of pericytes in blood-brain barrier injury under chronic cerebral hypoperfusion

doi:10.3969/j.issn.1006-7795.2018.04.012

Abstract

Abstract: Objective To investigate the effect of chronic cerebral hypoperfusion (CCH) on the blood-brain barrier (BBB) and pericytes. Methods Bilateral common carotid artery ligation (2-VO) rat model was used. Cerebral blood flow (CBF) was measured at the 3rd, 14th and 30th day after 2-VO surgery. Pericyte and fibrinogen expression were detected by fluorescence immunohistochemistry. Primary cultured pericytes were subjected to cell proliferation experiments. Transmission electron microscopy was used to observe the ultrastructure of blood-brain barrier. Results CBF was decreased in each model group, and kept lower at 30th day after 2-VO. BBB was damaged with fibrin(ogen) extravascular leakage, thickening of the basement membrane, dense deposit in the extravascular space, astrocyte edema, and red blood cell extravascular leakage. The number of pericytes was increased on the 3rd, 14th, and 30th day after surgery. In vitro, low concentration of fibrinogen could promote the proliferation of pericytes, while high concentration (20mg/mL) of fibrinogen had toxic effects on the pericytes. Conclusion CCH disrupts the BBB accompanying with pericytes proliferation, and fibrinogen exudation may be the main cause of pericyte hyperplasia.

Key words: chronic cerebral hypoperfusion, blood-brain barrier, pericyte, fibrinogen

CLC Number:

R743.31

Cao Dandan, Sun Jing, Bai Yunfei, Wang Miao, Guo Chenjia, Cui Jing, Li Liang. Role of pericytes in blood-brain barrier injury under chronic cerebral hypoperfusion[J]. Journal of Capital Medical University, 2018, 39(4): 541-545.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2018.04.012

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2018/V39/I4/541

References

[1] Yang T, Sun Y, Lu Z Y, et al. The impact of cerebrovascular aging on vascular cognitive impairment and dementia[J]. Ageing Res Rev, 2017, 34(3):15-29.
[2] Attwell D, Mishra A, Hall C N, et al. What is a pericyte?[J]. Cereb Blood Flow Metab, 2016, 36(2):451-455.
[3] Farkas E, Luiten P G, Bari F. Permanent, bilateral common carotid artery occlusion in the rat:a model for chronic cerebral hypoperfusion-related neurodegenerative diseases[J]. Brain Res Rev, 2007, 54(1):162-180.
[4] Cao D D, Bai Y F, Li L. Common carotid arteries occlusion surgery in adult rats as a model of chronic cerebral hypoperfusion[J]. Bio Protoc, 2018,8(2):e2704.
[5] Yang Y, Salayandia V M, Thompson J F, et al. Attenuation of acute stroke injury in rat brain by minocycline promotes blood-brain barrier remodeling and alternative microglia/macrophage activation during recovery[J]. J Neuroinflammation,2015, 12-26.
[6] Zha Y F, Fu X Z, Zhang S, et al. Establishment of an in vitro blood-brain barrier model by co-culturing rat brain microvascular endothelial cells, pericytes and astrocytes[J]. Chinese Pha Bulletin, 2015, 31(5):730-735.
[7] AbbOtt N J,Ronnback L,Hansson E N, et al.Astrocyte-endothelial interactions at the blood-brain barrier[J].Nat Rev Neurosci, 2006, 7(1):41-53.
[8] Ma X L, Gao F, Nelson A H, et al. Oxidative inactivation of nitric oxide and endothelial dysfunction in stroke-prone spontaneous hypertensive rats[J]. J Pharmacol Exp Ther,2001, 298(3):879-885.
[9] Rouhl R P, Damoiseaux J G, Lodder J, et al. Vascular inflammation in cerebral small vessel disease[J]. Neurobiol Aging, 2012, 33(8):1800-1806.
[10] Elali A, Theriault P, Rivest S. The role of pericytes in neurovascular unit remodeling in brain disorders[J]. Int J Mol Sci, 2014, 15(4):6453-6474.
[11] Winkler E A, Bell R D, Zlokovic B V. Central nervous system pericytes in health and disease[J]. Nat Neurosci, 2011, 14(11):1398-1405.
[12] Guimaraes-camboa N, Cattaneo P, SUN Y, et al. Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo[J]. Cell Stem Cell, 2017, 20(3):345-359.
[13] Hall C N, Reynell C, Gesslein B, et al. Capillary pericytes regulate cerebral blood flow in health and disease[J]. Nature, 2014, 508(7494):55-60.
[14] Axel M, Angeliki M N, Zhao Z, et al. Pericyte degeneration causes white matter dysfunction in the mouse central nervous system[J]. Nat Med, 2018, 24(3):326-337.
[15] Takashi M, Shinya D, Fuyuko T, et al. Role of thrombin-PAR1-PKC^θ/δ axis in brain pericytes in thrombin-induced MMP-9 production and blood-brain barrier dysfunction in vitro[J]. Neurosci, 2017, 350(1):146-157.
[16] Satish S, Houng A K, Reed G L. Matrix metalloproteinase-9 mediates the deleterious effects of α2-antiplasmin on blood-brain barrier breakdown and ischemic brain injury in experimental stroke[J]. Neuroscience,2018, 376(1):40-47.
[17] 任思颖, 伍国锋,杨勤,等.病灶区灌注罗格列酮对脑出血家兔血肿周围咬合蛋白和闭合小环蛋白1 mRNA表达水平及血-脑屏障通透性的影响[J].中国脑血管病杂志,2017,14(11):580-584,593.
[18] 申杰,朱润秀,袁军,等.血小板源性生长因子受体-β对局灶性脑缺血小鼠血-脑屏障通透性的影响[J].中国脑血管病杂志,2016,13(11):593-600.