Abstracts

Rationale: Despite recent advances in perinatal care, neonatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of neonatal mortality and neurologic morbidities. Our aim was to determine whether human mesenchymal stem cells (MSC) transplantation can improve brain injury and result neurotrophic and anti-inflammatory effects in a neonatal HIE rat model. Methods: A HIE rat model was induced by of right common carotid artery in 7-day-old rats and followed by 2.5 h of exposure to 8% oxygen. Three days after the HIE insult, rats received a stereotaxic bilateral intracranial injection of hMSCs. After 24 hours, mRNA expression of brain-derived neurotrophic factor (BDNF), Proliferating cell nuclear antigen (PCNA), Interleukin-1 beta (IL-1ß) were measured in the following groups of animals : HIE+high MSCs (4 µL * 10⁵ cells/µL), HIE+low MSCs (4 µL * 10⁴ cells/µL), and HIE+ Dulbecco's modified essential medium (DMEM, 4 µL) group. Comparisons of area in both hemispheres and hippocampi were done. Results: The group of HIE+high MSCs showed significant high BDNF (P=0.029), no difference in PCNA and IL-1ß (P=0.262 / 0.203). The rates of infarction inter-hemispheric / hippocampal area were lower in rats injected with high MSCs comparing to low MSCs and DMEM group (P=0.039 / 0.047).  Conclusions: This study suggests that high dose of MSCs can induce expression of BDNF and be used as a valuable source to improve outcome in HIE. Further study is necessary to identify the optimal time and dose that shows maximal efficacy for HIE treatment. Funding: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare (HI15C0810).