Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis.
Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (P<0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P>0.05) and most of them were differentiated into glial fibrillary acidic protein(+) (GFAP(+)) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (P<0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia.
Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
Yaohui
Y
Tang
Department of Neurology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Jixian
J
Wang
Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
Xiaojie
X
Lin
Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research the First Affiliated Hospital, Department of Neurology, Wenzhou Medical College, Zhejiang, China.
Liuqing
L
Wang
Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research the First Affiliated Hospital, Department of Neurology, Wenzhou Medical College, Zhejiang, China.
Bei
B
Shao
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Kunlin
K
Jin
Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
Yongting
Y
Wang
1] Neuroscience and Neuroengineering Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China [2] Department of Neurology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Guo-Yuan
GY
Yang
D000375:Aging; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D006085:Graft Survival; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D058953:Neural Stem Cells / Q000637:transplantation*; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000473:pathology*; D033581:Stem Cell Transplantation / Q000379:methods; D020521:Stroke / Q000473:pathology