PMID- 22791305 OWN - NLM STAT- MEDLINE DCOM- 20130415 LR - 20181201 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 90 IP - 11 DP - 2012 Nov TI - Intracerebral transplantation of bone marrow stromal cells ameliorates tissue plasminogen activator-induced brain damage after cerebral ischemia in mice detected by in vivo and ex vivo optical imaging. PG - 2086-93 LID - 10.1002/jnr.23104 [doi] AB - Detection and protection of the neurovascular unit (NVU) are essential for treatment of acute stroke patients, especially the use of tissue plasminogen activator (tPA). In the present study, we conducted in vivo and ex vivo optical imaging for detecting activation of matrix metalloproteinases (MMPs) and evaluated the protective effect of intracerebral transplantation of bone marrow stromal cells (BMSCs) obtained from green fluorescent protein (GFP) transgenic (Tg) mice on the NVU in tPA-mediated brain damage after transient middle cerebral artery occlusion (tMCAO) in mice. Compared with the tMCAO group, the tMCAO plus BMSC group showed significant reductions of in vivo and ex vivo fluorescent signals for MMPs at 48 hr after tMCAO, with a partial colocalization of BMSC-GFP signals. Intracerebrally transplanted BMSCs ameliorated MMP-9 activation by immunohistochemistry and Western blot with differentiation into microglial and astroglial cells. Double-immunofluorescence study revealed improved NVU disruption in the tMCAO plus BMSC group. The present study suggests that intracerebral BMSC transplantation reduced MMP activation and subsequent NVU disruption caused by tPA after tMCAO and that this MMP activation and BMSC effect were detectable with in vivo and ex vivo optical imaging. CI - Copyright (c) 2012 Wiley Periodicals, Inc. FAU - Liu, Ning AU - Liu N AD - Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. FAU - Deguchi, Kentaro AU - Deguchi K FAU - Yamashita, Toru AU - Yamashita T FAU - Liu, Wentao AU - Liu W FAU - Ikeda, Yoshio AU - Ikeda Y FAU - Abe, Koji AU - Abe K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120713 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Fibrinolytic Agents) RN - EC 3.4.21.68 (Tissue Plasminogen Activator) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Blotting, Western MH - *Bone Marrow Transplantation MH - Brain Ischemia/metabolism/*therapy MH - Cerebral Hemorrhage/chemically induced/therapy MH - Enzyme Activation/drug effects MH - Fibrinolytic Agents/*toxicity MH - Fluorescent Antibody Technique MH - Male MH - Matrix Metalloproteinases/biosynthesis MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Optical Imaging MH - Tissue Plasminogen Activator/*toxicity EDAT- 2012/07/14 06:00 MHDA- 2013/04/16 06:00 CRDT- 2012/07/14 06:00 PHST- 2012/03/13 00:00 [received] PHST- 2012/05/04 00:00 [revised] PHST- 2012/05/24 00:00 [accepted] PHST- 2012/07/14 06:00 [entrez] PHST- 2012/07/14 06:00 [pubmed] PHST- 2013/04/16 06:00 [medline] AID - 10.1002/jnr.23104 [doi] PST - ppublish SO - J Neurosci Res. 2012 Nov;90(11):2086-93. doi: 10.1002/jnr.23104. Epub 2012 Jul 13.