Neural Stem Cells Expressing bFGF Reduce Brain Damage and Restore Sensorimotor Function after Neonatal Hypoxia-Ischemia

Background/Aims: Neonatal hypoxia-ischemia (HI) causes severe brain damage and significantly increases neonatal morbidity and mortality. Increasing evidences have verified that stem cell-based therapy has the potential to rescue the ischemic tissue and restore function via secreting growth factors after HI. Here, we had investigated whether intranasal neural stem cells (NSCs) treatment improves the recovery of neonatal HI, and NSCs overexpressing basic fibroblast growth factor (bFGF) has a better therapeutic effect for recovery than NSCs treatment only. Methods: We performed permanent occlusion of the right common carotid artery in 9-day old ICR mice as animal model of neonatal hypoxia-ischemia. At 3 days post-HI, NSC, NSC-GFP, NSC-bFGF and vehicle were delivered intranasally. To determine the effect of intranasal NSC, NSC-GFP and NSC-bFGF treatment on recovery after HI, we analyzed brain damage, sensor-motor function and cell differentiation. Results: It was observed that intranasal NSC, NSC-GFP and NSC-bFGF treatment decreased gray and white matter loss area in comparison with vehicle-treated mouse. NSC, NSC-GFP and NSC-bFGF treatment also significantly improved sensor motor function in cylinder rearing test and adhesive removal test, however, NSC-bFGF-treatment was more effective than NSC-treatment in the improvement of somatosensory function. Furthermore, compared with NSC and NSC-GFP, NSC-bFGF treatment group appeared to differentiate into more neurons. Conclusion: Taken together, intranasal administration of NSCs is a promising therapy for treatment of neonatal HI, but NSCs overexpressing bFGF promotes the survival and differentiation of NSCs, and consequently achieves a better therapeutic effect in improving recovery after neonatal HI.

Download Full-text

Brain damage caused by neonatal hypoxia-ischemia and the effects of hypothermia in severe combined immunodeficient (SCID) mice

Experimental Neurology ◽

10.1016/j.expneurol.2020.113577 ◽

2021 ◽

Vol 337 ◽

pp. 113577

Author(s):

Yuko Ogawa ◽

Emi Tanaka ◽

Yoshiaki Sato ◽

Masahiro Tsuji

Keyword(s):

Brain Damage ◽

Scid Mice ◽

Neonatal Hypoxia ◽

Hypoxia Ischemia

Download Full-text

Therapeutic effect of genetically modified human neural stem cells encoding cytosine deaminase on experimental glioma

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2011.11.155 ◽

2012 ◽

Vol 417 (1) ◽

pp. 534-540 ◽

Cited By ~ 22

Author(s):

Jae Ho Kim ◽

Jin Young Kim ◽

Seung U. Kim ◽

Kyung Gi Cho

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Therapeutic Effect ◽

Genetically Modified ◽

Cytosine Deaminase ◽

Human Neural Stem Cells ◽

Experimental Glioma

Download Full-text

Sensitive-stage embryo irradiation affects embryonic neuroblasts and adult motor function

Molecular & Cellular Toxicology ◽

10.1007/s13273-021-00212-y ◽

2022 ◽

Author(s):

Ram Wagle ◽

Young-Han Song

Keyword(s):

Stem Cells ◽

Cell Death ◽

Neural Stem Cells ◽

Motor Function ◽

Radiation Sensitivity ◽

Embryonic Lethality ◽

Apoptotic Cells ◽

Childhood Malignancies ◽

Sensitive Stage ◽

Stage Embryo

Abstract Background Cranial radiation therapy for treating childhood malignancies in the central nervous system or accidental radiation exposure may result in neurological side effects in surviving adults. As tissue homeostasis is maintained by stem cells, understanding the effect of radiation on neural stem cells will provide clues for managing the neurological effects. Drosophila embryos were used as a model system whose sensitivity to irradiation-induced cell death changes from the sensitive to resistant stage during development. Objective Drosophila embryos at the radiation-sensitive stage were irradiated at various doses and the radiation sensitivity was tested regarding the appearance of apoptotic cells in the embryos and the embryonic lethality. Cell fates of the neural stem cells called neuroblasts (NBs) and adult motor function after irradiation were also investigated. Result Irradiation of Drosophila embryos at the radiation-sensitive stage resulted in a dose-dependent increase in the number of embryos containing apoptotic cells 75 min after treatment starting at 3 Gy. Embryonic lethality assayed by hatch rate was induced by 1 Gy irradiation, which did not induce cell death. Notably, no apoptosis was detected in NBs up to 2 h after irradiation at doses as high as 40 Gy. At 3 h after irradiation, as low as 3 Gy, the number of NBs marked by Dpn and Klu was decreased by an unidentified mechanism regardless of the cell death status of the embryo. Furthermore, embryonic irradiation at 3 Gy, but not 1 Gy, resulted in locomotor defects in surviving adults. Conclusion Embryonic NBs survived irradiation at doses as high as 40 Gy, while cells in other parts of the embryos underwent apoptosis at doses higher than 3 Gy within 2 h after treatment. Three hours after exposure to a minimum dose of 3 Gy, the number of NBs marked by Dpn and Klu decreased, and the surviving adults exhibited defects in locomotor ability.

Download Full-text