PMID- 24284395 OWN - NLM STAT- MEDLINE DCOM- 20140603 LR - 20211021 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 14 IP - 11 DP - 2013 Nov 11 TI - Combination BMSC and Niaspan treatment of stroke enhances white matter remodeling and synaptic protein expression in diabetic rats. PG - 22221-32 LID - 10.3390/ijms141122221 [doi] AB - 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. FAU - Ye, Xinchun AU - Ye X AD - Department of Neurology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. jieli@neuro.hfh.edu. FAU - Yan, Tao AU - Yan T FAU - Chopp, Michael AU - Chopp M FAU - Zacharek, Alex AU - Zacharek A FAU - Ning, Ruizhuo AU - Ning R FAU - Venkat, Poornima AU - Venkat P FAU - Roberts, Cynthia AU - Roberts C FAU - Chen, Jieli AU - Chen J LA - eng GR - R01 AG031811/AG/NIA NIH HHS/United States GR - R41 NS064708/NS/NINDS NIH HHS/United States GR - 1R41NS064708/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131111 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Lipoproteins, HDL) RN - 2679MF687A (Niacin) SB - IM MH - Animals MH - Brain/drug effects/pathology/*ultrastructure MH - Diabetes Mellitus, Experimental/complications/metabolism MH - Diabetes Mellitus, Type 1/metabolism/pathology MH - Lipoproteins, HDL/biosynthesis MH - *Mesenchymal Stem Cells MH - Niacin/*administration & dosage MH - *Protein Biosynthesis MH - Rats MH - Stroke/*drug therapy/metabolism/pathology MH - Synapses/genetics/metabolism/ultrastructure PMC - PMC3856061 EDAT- 2013/11/29 06:00 MHDA- 2014/06/04 06:00 PMCR- 2013/11/01 CRDT- 2013/11/29 06:00 PHST- 2013/08/01 00:00 [received] PHST- 2013/10/16 00:00 [revised] PHST- 2013/10/18 00:00 [accepted] PHST- 2013/11/29 06:00 [entrez] PHST- 2013/11/29 06:00 [pubmed] PHST- 2014/06/04 06:00 [medline] PHST- 2013/11/01 00:00 [pmc-release] AID - ijms141122221 [pii] AID - ijms-14-22221 [pii] AID - 10.3390/ijms141122221 [doi] PST - epublish SO - Int J Mol Sci. 2013 Nov 11;14(11):22221-32. doi: 10.3390/ijms141122221.