Abstracts

Rationale: Despite recent advances in perinatal care, neonatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of neonatal mortality and neurologic morbidities including epilepsy. Our aim was to determine whether human embryonal cell derived neural progenitor cells (NPC) 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 coagulation of right common carotid artery and followed by 2 hours of exposure to 8% oxygen in 7-day-old rats. After half a day of the HIE insult, rats received a stereotaxic bilateral intracranial injection of NPCs. After 24 hours, infarction rate by coronal different area between both hemispheres and hippocampi, mRNA expression of brain-derived neurotrophic factor (BDNF), Proliferating cell nuclear antigen (PCNA) and Interleukin-1 beta (IL-1β) were measured in the following 4 groups of animals : HIE+high dose NPCs (4 µL * 105 cells/µL), HIE+low dose NPCs (4 µL * 104 cells/µL), HIE+ Dulbecco's modified essential medium (DMEM, 4 µL), and Sham (not HIE) group. Comparisons of area in both hemispheres and hippocampi were done. Results: The group of HIE+high dose NPCs showed significant high BDNF (P=0.00007), PCNA (P=0.000222) and IL-1β (P=0.000000). The rate of inter-hemispheric infarction were lower in rats injected with high dose NPCs comparing to low dose NPCs and DMEM group (P=0.039), and hippocampal infarction rate (P=0.047). Conclusions: This study suggests that high dose transplantation of NPCs can induce expression of BDNF, PCNA 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: No funding