Neural Regeneration Research ›› 2014, Vol. 9 ›› Issue (19): 1745-1752.doi: 10.4103/1673-5374.143417

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Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy: neuroprotective effects of combined therapy

Lin Wang, Feng Jiang, Qifeng Li, Xiaoguang He, Jie Ma   

  1. Department of Pediatric Neurosurgery, Xinhua Hospital of Shanghai Jiaotong University, Shanghai 200092, China
  • Received:2014-09-15 Online:2014-10-15 Published:2014-10-15
  • Contact: Jie Ma, Ph.D., M.D., Department of Pediatric Neurosurgery, Xinhua Hospital of Shanghai Jiaotong University, Shanghai 200092, China, majie365@hotmail.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81271382.

Abstract:

Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27–28°C) can increase the survival rate of neural stem cells (1.0 × 105 /μL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hypothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and anti-apoptotic mechanisms.

Key words: nerve regeneration, brain injury, hypoxic-ischemic encephalopathy, neural precursor cells, hypothermia, neural stem cells, cell transplantation, hippocampus, neuron, cell apoptosis, astrocytes, oligodendrocytes, neuroprotection, NSFC grants, neural regeneration