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Combination BMSC and Niaspan Treatment of Stroke Enhances White Matter Remodeling and Synaptic Protein Expression in Diabetic Rats
Department of Neurology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China
Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA
Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin 300052, China
Department of Physics, Oakland University, Rochester, MI 48309, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 1 August 2013; in revised form: 16 October 2013 / Accepted: 18 October 2013 / Published: 11 November 2013
Abstract: Objective: White matter remodeling plays an important role in neurological recovery after stroke. Bone marrow stromal cells (BMSCs) and Niaspan, an agent which increases high density lipoprotein (HDL), each induces neurorestorative effects and promotes white matter remodeling after stroke in non-diabetic rats. In this study, we test whether combination of BMSCs with Niaspan induces an enhanced white matter remodeling in the ischemic brain of diabetic rats. Research design and methods: Type-1 diabetes (T1DM) rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated with or without BMSCs; Niaspan; and the combination of BMSCs + Niaspan daily for 14 days after MCAo. Immunostaining for white matter remodeling and synaptic protein expression including NG2; CNPase; BS (Bielschowsky silver); LFB (luxol fast blue); Synaptophysin and SMI-31 immunostaining were performed. Results: BMSC monotherapy did not regulate NG2 and CNPase expression compared to T1DM control rats. Both, combination of BMSCs + Niaspan treatment, and Niaspan monotherapy significantly increase NG2 and CNPase expression compared to T1DM control. While combination BMSC+Niaspan, BMSC monotherapy and Niaspan monotherapy groups all increase BS, LFB, synaptophysin, and SMI-31 expression in the ischemic brain compared to T1DM-MCAo control. In addition, the combination treatment significantly enhances LFB, SMI-31, and Synaptophysin expression compared to BMSC monotherapy. Conclusions: Combination treatment of stroke with BMSCs and Niaspan in T1DM rats increases white matter remodeling and additively increases BMSC monotherapy induced myelination and synaptic plasticity after stroke in T1DM rats.
Keywords: type-one diabetic rats; stroke; bone marrow stromal cells; Niaspan; white matter remodeling; synaptic plasticity
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Ye, X.; Yan, T.; Chopp, M.; Zacharek, A.; Ning, R.; Venkat, P.; Roberts, C.; Chen, J. Combination BMSC and Niaspan Treatment of Stroke Enhances White Matter Remodeling and Synaptic Protein Expression in Diabetic Rats. Int. J. Mol. Sci. 2013, 14, 22221-22232.
Ye X, Yan T, Chopp M, Zacharek A, Ning R, Venkat P, Roberts C, Chen J. Combination BMSC and Niaspan Treatment of Stroke Enhances White Matter Remodeling and Synaptic Protein Expression in Diabetic Rats. International Journal of Molecular Sciences. 2013; 14(11):22221-22232.
Ye, Xinchun; Yan, Tao; Chopp, Michael; Zacharek, Alex; Ning, Ruizhuo; Venkat, Poornima; Roberts, Cynthia; Chen, Jieli. 2013. "Combination BMSC and Niaspan Treatment of Stroke Enhances White Matter Remodeling and Synaptic Protein Expression in Diabetic Rats." Int. J. Mol. Sci. 14, no. 11: 22221-22232.