Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia

Major Points and Findings:

1. Objective: The study aimed to understand the potential benefits of F3.olig2 cells in improving neurobehavioral deficits in a model of PVL.
2. Methodology: Seven-day-old male rats were subjected to a combination of hypoxia-ischemia and lipopolysaccharide injection (HIL). These rats were then intracerebroventricularly transplanted with F3.olig2 cells either once at post-natal day (PND) 10 or repeatedly at PND10, 17, 27, and 37.
3. Neurobehavioral Assessments: The neurobehavioral disorders in the rats were evaluated at various post-natal days (PND14, 20, 30, and 40) using tests like the cylinder test, locomotor activity, and rotarod performance. Additionally, cognitive function was assessed at PND41-45 through passive avoidance and Morris water-maze performances.
4. Results:
   • F3.olig2 cells aided in the recovery of the use rate of the forelimb contralateral to the injured brain.
   • There was an improvement in locomotor activity and rotarod performance in PVL animals.
   • A significant enhancement in learning and memory function was observed.
   • Transplanted F3.olig2 cells were found to migrate to injured areas, mature into oligodendrocytes expressing myelin basic protein (MBP), and significantly reduce the loss of host MBP in the corpus callosum.
5. Conclusion: The transplanted F3.olig2 cells were effective in restoring neurobehavioral functions by preventing axonal demyelination. This suggests that human oligodendrocyte progenitor cells could be potential candidates for cell therapy in treating perinatal hypoxic-ischemic and infectious brain injuries, including PVL and cerebral palsy.

The study provides valuable insights into the potential therapeutic benefits of human oligodendrocyte progenitor cells in treating neurobehavioral disorders associated with PVL.