title: Autologous Bone Marrow Mononuclear Cells Exert Broad Effects on Short- and Long-Term Biological and Functional Outcomes in Rodents with Intracerebral Hemorrhage.
abstract: Autologous bone marrow-derived mononuclear cells (MNCs) are a potential therapy for ischemic stroke. However, the effect of MNCs in intracerebral hemorrhage (ICH) has not been fully studied. In this study, we investigated the effects of autologous MNCs in experimental ICH. ICH was induced by infusion of autologous blood into the left striatum in young and aged male Long Evans rats. Twenty-four hours after ICH, rats were randomized to receive an intravenous administration of autologous MNCs (1 × 10(7) cells/kg) or saline. We examined brain water content, various markers related to the integrity of the neurovascular unit and inflammation, neurological deficit, neuroregeneration, and brain atrophy. We found that MNC-treated young rats showed a reduction in the neurotrophil infiltration, the number of inducible nitric oxide synthase-positive cells, and the expression of inflammatory-related signalings such as the high-mobility group protein box-1, S100 calcium binding protein B, matrix metalloproteinase-9, and aquaporin 4. Ultimately, MNCs reduced brain edema in the perihematomal area compared with saline-treated animals at 3 days after ICH. Moreover, MNCs increased vessel density and migration of doublecortin-positive cells, improved motor functional recovery, spatial learning, and memory impairment, and reduced brain atrophy compared with saline-treated animals at 28 days after ICH. We also found that MNCs reduced brain edema and brain atrophy and improved spatial learning and memory in aged rats after ICH. We conclude that autologous MNCs can be safely harvested and intravenously reinfused in rodent ICH and may improve long-term structural and functional recovery after ICH. The results of this study may be applicable when considering future clinical trials testing MNCs for ICH.
authors.affiliation: 1 Department of Neurological Science, Graduate School of Medicine, Nippon Medical School , Tokyo, Japan .
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suda
authors.affiliation: 2 Department of Neurology, University of Texas Medical School at Houston , Houston, Texas.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: 2 Department of Neurology, University of Texas Medical School at Houston , Houston, Texas.
authors.forename: Krystal
authors.initials: K
authors.lastname: Schaar
authors.affiliation: 2 Department of Neurology, University of Texas Medical School at Houston , Houston, Texas.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Xi
authors.affiliation: 2 Department of Neurology, University of Texas Medical School at Houston , Houston, Texas.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pido
authors.affiliation: 2 Department of Neurology, University of Texas Medical School at Houston , Houston, Texas.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Parsha
authors.affiliation: 2 Department of Neurology, University of Texas Medical School at Houston , Houston, Texas.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Aronowski
authors.affiliation: 2 Department of Neurology, University of Texas Medical School at Houston , Houston, Texas.
authors.forename: Sean I
authors.initials: SI
authors.lastname: Savitz
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000628:therapy*; D000089662:Doublecortin Protein; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008568:Memory; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D020318:Rats, Long-Evans; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D014182:Transplantation, Autologous
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D009418:S100 Proteins; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat