title: Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells.
abstract: Brain damage around birth may cause lifelong neurodevelopmental deficits. We examined the therapeutic potential of human umbilical cord blood-derived mononuclear cells containing multipotent stem cells to facilitate motor recovery after cerebral hypoxic-ischemic damage in neonatal rats. Left carotid artery ligation followed by 8% O(2) inhalation for 80 min was performed on postnatal d 7, succeeded by intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells on postnatal d 8 in a sham-controlled design. Histologic and immunohistochemical analysis on postnatal d 21 revealed that neonates developed severe cerebral damage after the hypoxic-ischemic insult. These animals also suffered from contralateral spastic paresis, as evidenced by their locomotor behavior. After transplantation of human umbilical cord blood-derived mononuclear cells, spastic paresis was largely alleviated, resulting in a normal walking behavior. This "therapeutic" effect was accompanied by the fact that mononuclear cells had entered the brain and were incorporated around the lesion without obvious signs of transdifferentiation. This study demonstrates that intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells in a rat model of perinatal brain damage leads to both incorporation of these cells in the lesioned brain area and to an alleviation of the neurologic effects of cerebral palsy as assessed by footprint and walking pattern analysis.
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-University Bochum, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Meier
authors.forename: Johannes
authors.initials: J
authors.lastname: Middelanis
authors.forename: Bianca
authors.initials: B
authors.lastname: Wasielewski
authors.forename: Sandra
authors.initials: S
authors.lastname: Neuhoff
authors.forename: Astrid
authors.initials: A
authors.lastname: Roth-Haerer
authors.forename: Markus
authors.initials: M
authors.lastname: Gantert
authors.forename: Hubert R
authors.initials: HR
authors.lastname: Dinse
authors.forename: Rolf
authors.initials: R
authors.lastname: Dermietzel
authors.forename: Arne
authors.initials: A
authors.lastname: Jensen
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology; D009000:Monocytes / Q000637:transplantation*; D020336:Paraparesis, Spastic / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D016138:Walking