Niaspan Attenuates the Adverse Effects of Bone Marrow Stromal Cell Treatment of Stroke in Type One Diabetic Rats

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Dec 5

PMID 24303036

Citations 15

Authors

Tao Yan

XinChun Ye

Michael Chopp

Alex Zacharek

Ruizhuo Ning

Poornima Venkat

Cynthia Roberts

Mei Lu

Jieli Chen

Affiliations

Soon will be listed here.

Abstract

Aims: Our previous studies have found that bone-marrow-stromal cells (BMSC) therapy improves functional recovery after stroke in non-diabetic rats while increases brain hemorrhage and induces arteriosclerosis-like changes in type-one-diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats.

Methods: T1DM-rats induced by streptozotocin were subjected to 2 hours of middle-cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5×10(6)); 3) Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5×10(6)) +Niaspan (40 mg/kg, daily for 14 days) combination starting at 24 hours after MCAo. All rats were monitored for 14 days.

Results: Combination BMSC+Niaspan treatment of T1DM-MCAo rats did not increase brain hemorrhage, and significantly decreased BBB leakage and vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal-carotid-artery compared to non-treatment control and BMSC monotherapy animals.

Conclusions: Combination therapy using BMSC with Niaspan decreases BBB leakage and cerebral arteriosclerosis-like changes. These beneficial effects may be attributed to the decreased expression of Angiogenin, MMP9 and ED1.

Citing Articles

Challenges and Improvements of Novel Therapies for Ischemic Stroke.

Yang L, Qian J, Yang B, He Q, Wang J, Weng Q Front Pharmacol. 2021; 12:721156.

PMID: 34658860 PMC: 8514732. DOI: 10.3389/fphar.2021.721156.

Human amniotic fluid stem cells can improve cerebral vascular remodelling and neurological function after focal cerebral ischaemia in diabetic rats.

Liang C, Shaw S, Huang Y, Lee T J Cell Mol Med. 2021; 25(21):10185-10196.

PMID: 34622573 PMC: 8572791. DOI: 10.1111/jcmm.16956.

Melatonin protects against focal cerebral ischemia-reperfusion injury in diabetic mice by ameliorating mitochondrial impairments: involvement of the Akt-SIRT3-SOD2 signaling pathway.

Liu L, Cao Q, Gao W, Li B, Xia Z, Zhao B Aging (Albany NY). 2021; 13(12):16105-16123.

PMID: 34118791 PMC: 8266371. DOI: 10.18632/aging.203137.

The Effects and Underlying Mechanisms of Cell Therapy on Blood-Brain Barrier Integrity After Ischemic Stroke.

Gao L, Song Z, Mi J, Hou P, Xie C, Shi J Curr Neuropharmacol. 2020; 18(12):1213-1226.

PMID: 32928089 PMC: 7770640. DOI: 10.2174/1570159X18666200914162013.

Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury.

Willing A, Das M, Howell M, Mohapatra S, Mohapatra S CNS Neurosci Ther. 2020; 26(6):616-627.

PMID: 32157822 PMC: 7248546. DOI: 10.1111/cns.13300.

References

Montecucco F, Quercioli A, Dallegri F, Viviani G, Mach F . New evidence for nicotinic acid treatment to reduce atherosclerosis. Expert Rev Cardiovasc Ther. 2010; 8(10):1457-67. DOI: 10.1586/erc.10.116. View

Ye X, Chopp M, Cui X, Zacharek A, Cui Y, Yan T . Niaspan enhances vascular remodeling after stroke in type 1 diabetic rats. Exp Neurol. 2011; 232(2):299-308. PMC: 3265018. DOI: 10.1016/j.expneurol.2011.09.022. View

Huang J, Upadhyay U, Tamargo R . Inflammation in stroke and focal cerebral ischemia. Surg Neurol. 2006; 66(3):232-45. DOI: 10.1016/j.surneu.2005.12.028. View

Hernandez T, Schallert T . Seizures and recovery from experimental brain damage. Exp Neurol. 1988; 102(3):318-24. DOI: 10.1016/0014-4886(88)90226-9. View

Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M . Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke. 2001; 32(4):1005-11. DOI: 10.1161/01.str.32.4.1005. View

Meyers C, Kamanna V, Kashyap M . Niacin therapy in atherosclerosis. Curr Opin Lipidol. 2004; 15(6):659-65. DOI: 10.1097/00041433-200412000-00006. View

Malamitsi-Puchner A, Sarandakou A, Dafogianni C, Tziotis J, Bartsocas C . Serum angiogenin levels in children and adolescents with insulin-dependent diabetes mellitus. Pediatr Res. 1998; 43(6):798-800. DOI: 10.1203/00006450-199806000-00013. View

Strydom D . The angiogenins. Cell Mol Life Sci. 1998; 54(8):811-24. PMC: 11147295. DOI: 10.1007/s000180050210. View

Basu A, Pal S, Saha S, Bandyopadhyay R, Mukherjee S, Sarkar P . Risk factor analysis in ischaemic stroke: a hospital-based study. J Indian Med Assoc. 2006; 103(11):586, 588. View

10.

Ganji S, Qin S, Zhang L, Kamanna V, Kashyap M . Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis. 2008; 202(1):68-75. DOI: 10.1016/j.atherosclerosis.2008.04.044. View

11.

Chen J, Ye X, Yan T, Zhang C, Yang X, Cui X . Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats. Stroke. 2011; 42(12):3551-8. PMC: 3264886. DOI: 10.1161/STROKEAHA.111.627174. View

12.

Hong Park C, Shin T, Lee H, Kim S, Lee W . Matrix metalloproteinase inhibitors attenuate neuroinflammation following focal cerebral ischemia in mice. Korean J Physiol Pharmacol. 2011; 15(2):115-22. PMC: 3104200. DOI: 10.4196/kjpp.2011.15.2.115. View

13.

Lucas S, Rothwell N, Gibson R . The role of inflammation in CNS injury and disease. Br J Pharmacol. 2006; 147 Suppl 1:S232-40. PMC: 1760754. DOI: 10.1038/sj.bjp.0706400. View

14.

Crop M, Baan C, Korevaar S, IJzermans J, Alwayn I, Weimar W . Donor-derived mesenchymal stem cells suppress alloreactivity of kidney transplant patients. Transplantation. 2009; 87(6):896-906. DOI: 10.1097/TP.0b013e31819b3d72. View

15.

Ho T, Rajkumar V, Black C, Abraham D, BAKER D . Increased angiogenic response but deficient arteriolization and abnormal microvessel ultrastructure in critical leg ischaemia. Br J Surg. 2006; 93(11):1368-76. DOI: 10.1002/bjs.5496. View

16.

Yan T, Chopp M, Ye X, Liu Z, Zacharek A, Cui Y . Niaspan increases axonal remodeling after stroke in type 1 diabetes rats. Neurobiol Dis. 2012; 46(1):157-64. PMC: 3335197. DOI: 10.1016/j.nbd.2012.01.001. View

17.

Lucivero V, Prontera M, Mezzapesa D, Petruzzellis M, Sancilio M, Tinelli A . Different roles of matrix metalloproteinases-2 and -9 after human ischaemic stroke. Neurol Sci. 2007; 28(4):165-70. DOI: 10.1007/s10072-007-0814-0. View

18.

Zucker S, Hymowitz M, Conner C, Zarrabi H, Hurewitz A, Matrisian L . Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Clinical and experimental applications. Ann N Y Acad Sci. 1999; 878:212-27. DOI: 10.1111/j.1749-6632.1999.tb07687.x. View

19.

Zacharek A, Chen J, Cui X, Li A, Li Y, Roberts C . Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke. J Cereb Blood Flow Metab. 2007; 27(10):1684-91. PMC: 2796470. DOI: 10.1038/sj.jcbfm.9600475. View

20.

Lu D, Mahmood A, Wang L, Li Y, Lu M, Chopp M . Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome. Neuroreport. 2001; 12(3):559-63. DOI: 10.1097/00001756-200103050-00025. View