title: Bone-marrow mononuclear cells reduce neurodegeneration in hippocampal CA1 layer after transient global ischemia in rats.
abstract: Global cerebral ischemia (GCI) results in death of the pyramidal neurons in the CA1 layer of the hippocampus. In this study we used the four-vessel occlusion (4VO) model of GCI to investigate a potential neuroprotective role of bone-marrow mononuclear cells (BMMCs) transplantation. BMMCs (3×10(7)) were injected through the carotid artery, 1 or 3 days after ischemia (DAI), and the number of cells undergoing degeneration was investigated in brains at 7 DAI. A significant decrease in the number of dying cells was observed in the treated group, compared to animals treated with saline. Biodistribution of the injected cells (1 or 3 DAI) was investigated by (99m)Technetium labeling of the BMMCs and subsequent image analysis 2h after transplantation. In addition, the presence of CellTrace(™)-labeled BMMCs was investigated in tissue sections of the hippocampal area of these transplanted animals. BMMCs treatment significantly reduced the number of FJ-C positive cells in the hippocampal CA1 layer at 7 DAI. We also observed a decrease in the number of activated microglia/macrophage (ED1-positive cells) in the BMMCs-treated group compared with the untreated group. Our data show that BMMCs are able to modulate the microglial response and reduce neurodegeneration in the CA1 layer.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. alane@biof.ufrj.br
authors.forename: Alane Bernardo
authors.initials: AB
authors.lastname: Ramos
authors.forename: Andréia
authors.initials: A
authors.lastname: Vasconcelos-Dos-Santos
authors.forename: Sergio Augusto
authors.initials: SA
authors.lastname: Lopes de Souza
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Rosado-de-Castro
authors.forename: Lea Mirian
authors.initials: LM
authors.lastname: Barbosa da Fonseca
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.forename: Wagner Monteiro
authors.initials: WM
authors.lastname: Cintra
authors.forename: Rosalia
authors.initials: R
authors.lastname: Mendez-Otero
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D002545:Brain Ischemia / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar