PMID- 26243222
OWN - NLM
STAT- MEDLINE
DCOM- 20151203
LR  - 20220408
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Print)
IS  - 0039-2499 (Linking)
VI  - 46
IP  - 9
DP  - 2015 Sep
TI  - Neurorestorative Therapy of Stroke in Type 2 Diabetes Mellitus Rats Treated With 
      Human Umbilical Cord Blood Cells.
PG  - 2599-606
LID - 10.1161/STROKEAHA.115.009870 [doi]
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus is a high-risk factor for ischemic 
      stroke. Diabetic stroke patients suffer worse outcomes, poor long-term recovery, 
      risk of recurrent strokes, and extensive vascular damage. We investigated the 
      neurorestorative effects and the underlying mechanisms of stroke treatment with 
      human umbilical cord blood cells (HUCBCs) in type 2 diabetes mellitus (T2DM) 
      rats. METHODS: Adult male T2DM rats were subjected to 2 hours of middle cerebral 
      artery occlusion (MCAo). Three days after MCAo, rats were treated via tail-vein 
      injection with (1) PBS and (2) HUCBCs (5x10(6)), n=10 per group. RESULTS: HUCBC 
      stroke treatment initiated 3 days after MCAo in T2DM rats did not significantly 
      decrease blood-brain barrier leakage (P=0.1) and lesion volume (P=0.078), but 
      significantly improved long-term functional outcome and decreased brain 
      hemorrhage (P<0.05) when compared with the PBS-treated T2DM MCAo control group. 
      HUCBC treatment significantly promoted white matter remodeling as indicated by 
      increased expression of Bielschowsky silver (axons marker), Luxol fast blue 
      (myelin marker), SMI-31 (neurofilament), and Synaptophysin in the ischemic border 
      zone. HUCBC promoted vascular remodeling and significantly increased arterial and 
      vascular density. HUCBC treatment of stroke in T2DM rats significantly increased 
      M2 macrophage polarization (increased M2 macrophage, CD163and CD 206; decreased 
      M1 macrophage, ED1 and inducible nitric oxide synthase expression) in the 
      ischemic brain compared with PBS-treated T2DM MCAo controls (P<0.05). HUCBC also 
      significantly decreased proinflammatory factors, that is, matrix 
      metalloproteinase 9, receptor for advanced glycation end products and toll-like 
      receptor 4 expression in the ischemic brain. CONCLUSIONS: HUCBC treatment 
      initiated 3 days after stroke significantly increased white matter and vascular 
      remodeling in the ischemic brain as well as decreased neuroinflammatory factor 
      expression in the ischemic brain in T2DM rats and promoted M2 macrophage 
      polarization. HUCBC reduction of neuroinflammation and increased vascular and 
      white matter axonal remodeling may contribute to the HUCBC-induced beneficial 
      effects in T2DM stroke rats.
CI  - (c) 2015 American Heart Association, Inc.
FAU - Yan, Tao
AU  - Yan T
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Venkat, Poornima
AU  - Venkat P
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Chopp, Michael
AU  - Chopp M
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Zacharek, Alex
AU  - Zacharek A
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Ning, Ruizhuo
AU  - Ning R
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Cui, Yisheng
AU  - Cui Y
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Roberts, Cynthia
AU  - Roberts C
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Kuzmin-Nichols, Nicole
AU  - Kuzmin-Nichols N
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Sanberg, Cyndy Davis
AU  - Sanberg CD
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.).
FAU - Chen, Jieli
AU  - Chen J
AD  - From the Department of Neurology, Henry Ford Hospital, Detroit, MI (T.Y., P.V., 
      M.C., A.Z., R.N., Y.C., C.R., J.C.); Tianjin Neurological Institute, Neurology of 
      Tianjin Medical University General Hospital, Tianjin, China (T.Y., J.C.); 
      Department of Physics, Oakland University, Rochester, MI (P.V., M.C.); and 
      Saneron CCEL Therapeutics Inc, Tampa, FL (N.K.-N., C.D.S.). jieli@neuro.hfh.edu.
LA  - eng
GR  - R01 AG 037506/AG/NIA NIH HHS/United States
GR  - R01AG031811/AG/NIA NIH HHS/United States
GR  - R01 AG031811/AG/NIA NIH HHS/United States
GR  - R41 NS080329/NS/NINDS NIH HHS/United States
GR  - R01NS083078-01A1/NS/NINDS NIH HHS/United States
GR  - R01 AG037506/AG/NIA NIH HHS/United States
GR  - R41NS080329-01A1/NS/NINDS NIH HHS/United States
GR  - R01 NS083078/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150804
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
SB  - IM
MH  - Animals
MH  - Brain Ischemia/etiology/*therapy
MH  - Cord Blood Stem Cell Transplantation/*methods
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Disease Models, Animal
MH  - Humans
MH  - Infarction, Middle Cerebral Artery/etiology/therapy
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Stroke/etiology/*therapy
PMC - PMC4550506
MID - NIHMS707985
OTO - NOTNLM
OT  - diabetes mellitus, type 2
OT  - human umbilical cord blood
OT  - infarction, middle cerebral artery
OT  - matrix metalloproteinase 9
OT  - neurorestorative therapy
OT  - stroke
OT  - vascular remodeling
EDAT- 2015/08/06 06:00
MHDA- 2015/12/15 06:00
PMCR- 2016/09/01
CRDT- 2015/08/06 06:00
PHST- 2015/04/24 00:00 [received]
PHST- 2015/07/07 00:00 [accepted]
PHST- 2015/08/06 06:00 [entrez]
PHST- 2015/08/06 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - STROKEAHA.115.009870 [pii]
AID - 10.1161/STROKEAHA.115.009870 [doi]
PST - ppublish
SO  - Stroke. 2015 Sep;46(9):2599-606. doi: 10.1161/STROKEAHA.115.009870. Epub 2015 Aug 
      4.