title: Systemic injection of CD34(+)-enriched human cord blood cells modulates poststroke neural and glial response in a sex-dependent manner in CD1 mice.
abstract: Stroke in the developing brain is an important cause of neurological morbidity. We determined the impact of human cord blood-derived CD34(+)-enriched mononuclear cells (CBSC) intraperitoneally injected 48 h after an ischemic stroke at postnatal day 12 by evaluating poststroke neurogenic niche proliferation, glial response, and recovery in CD1 mice. Percent brain atrophy was quantified from Nissl-stained sections. Density of BrdU, Iba-1, and GFAP staining were quantified in the dentate gyrus and the subventricular zone (SVZ). Immunohistochemistry for human nuclear antibody, human mitochondrial antibody, and human CD34(+) cells was done on injured and uninjured brains from CBSC- and vehicle-treated mice. Developmental neurobehavioral milestones were evaluated pre- and post-treatment. No significant differences in stroke severity were noted between CBSC and vehicle-treated injured animals. With a 1×10(5) CBSC dose, there was a significant increase in subgranular zone (SGZ) proliferation in the CBSC-versus vehicle-treated stroke-injured male mice. SVZ glial fibrillary acidic protein (GFAP) expression was increased contralaterally in injured females treated with CBSC but suppressed in injured males. Significant negative correlations between severity of the stroke-injury and spleen weights, and between spleen weights and SGZ proliferation, and a positive correlation between GFAP expression and severity of brain injury were noted in the vehicle-treated injured mice but not in the CBSC-treated mice. GFAP expression and SVZ proliferation were positively correlated. In conclusion, neurogenic niche proliferation and glial brain responses to CBSC after neonatal stroke may involve interactions with the spleen and are sex dependent.
authors.affiliation: 1 Department of Neurology and Developmental Medicine, Kennedy Krieger Research Institute , Baltimore, Maryland.
authors.forename: Shilpa D
authors.initials: SD
authors.lastname: Kadam
authors.forename: HuiGen
authors.initials: H
authors.lastname: Chen
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Markowitz
authors.forename: Saba
authors.initials: S
authors.lastname: Raja
authors.forename: Shanu
authors.initials: S
authors.lastname: George
authors.forename: Tatayana
authors.initials: T
authors.lastname: Verina
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Shotwell
authors.forename: Brett
authors.initials: B
authors.lastname: Loechelt
authors.forename: Michael V
authors.initials: MV
authors.lastname: Johnston
authors.forename: Naynesh
authors.initials: N
authors.lastname: Kamani
authors.forename: Ali
authors.initials: A
authors.lastname: Fatemi
authors.forename: Anne M
authors.initials: AM
authors.lastname: Comi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D036101:Cord Blood Stem Cell Transplantation; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005312:Fetal Blood; D005904:Glial Fibrillary Acidic Protein; D064593:Heterografts; D006801:Humans; D020547:Lateral Ventricles / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012727:Sex Characteristics; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse