Systemic injection of CD34+-enriched human cord Blood cells modulates poststroke neural and glial response in a sex-dependent manner in CD1 mice

Shilpa D. Kadam, Huigen Chen, Geoffrey J. Markowitz, Saba Raja, Shanu George, Elisabeth Shotwell, Brett Loechelt, Michael V Johnston, Naynesh Kamani, Ali Fatemi, Anne Marie Spalding Comi

Research output: Contribution to journalArticle

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 1×105 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.

Original languageEnglish (US)
Pages (from-to)51-66
Number of pages16
JournalStem Cells and Development
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2015

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Fetal Blood
Neuroglia
Blood Cells
Stroke
Glial Fibrillary Acidic Protein
Injections
Lateral Ventricles
Spleen
Brain
Weights and Measures
Antibodies
Dentate Gyrus
Bromodeoxyuridine
Brain Injuries
Atrophy
Immunohistochemistry
Staining and Labeling
Morbidity
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Systemic injection of CD34+-enriched human cord Blood cells modulates poststroke neural and glial response in a sex-dependent manner in CD1 mice. / Kadam, Shilpa D.; Chen, Huigen; Markowitz, Geoffrey J.; Raja, Saba; George, Shanu; Shotwell, Elisabeth; Loechelt, Brett; Johnston, Michael V; Kamani, Naynesh; Fatemi, Ali; Comi, Anne Marie Spalding.

In: Stem Cells and Development, Vol. 24, No. 1, 01.01.2015, p. 51-66.

Research output: Contribution to journalArticle

Kadam, Shilpa D. ; Chen, Huigen ; Markowitz, Geoffrey J. ; Raja, Saba ; George, Shanu ; Shotwell, Elisabeth ; Loechelt, Brett ; Johnston, Michael V ; Kamani, Naynesh ; Fatemi, Ali ; Comi, Anne Marie Spalding. / Systemic injection of CD34+-enriched human cord Blood cells modulates poststroke neural and glial response in a sex-dependent manner in CD1 mice. In: Stem Cells and Development. 2015 ; Vol. 24, No. 1. pp. 51-66.
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AU - Markowitz, Geoffrey J.

AU - Raja, Saba

AU - George, Shanu

AU - Shotwell, Elisabeth

AU - Loechelt, Brett

AU - Johnston, Michael V

AU - Kamani, Naynesh

AU - Fatemi, Ali

AU - Comi, Anne Marie Spalding

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N2 - 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 1×105 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.

AB - 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 1×105 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.

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