Prenatal white matter injury is a serious problem due to maternal
inflammation leading to postnatal disabilities. In this study, we used the
periventricular leukomalacia (PVL) model as a common prenatal white matter injury by maternal administration of
lipopolysaccharide (LPS). Neural stem cells (NSCs) have shown therapeutic ability in
neurological disorders through a different mechanism such as
immunomodulation. Here, we studied the preventive potential of NSCs following in utero
transplantation into the embryonic lateral ventricle in an LPS-induced white matter injury model. Pregnant animals were divided into three groups and received
phosphate buffered saline, LPS, or LPS + NSCs. The brains of offspring were obtained and evaluated by real-time polymerase chain reaction (PCR), immunohistochemy,
enzyme-linked
immunosorbent assay (ELISA),
terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling (TUNEL), and
caspase-3 activity assay. The LPS-induced maternal
inflammation degenerated the myelin sheath in the offspring periventricular region which was associated with an increased microglial number, oligodendrocytes degeneration, proinflammatory
cytokine secretion, and cell apoptosis. The transplanted NSCs homed into the brain and ameliorated the evaluated parameters. The expression of proinflammatory
cytokines interleukin-1β (IL-1β),
IL-6, and
tumor necrosis factor-α (TNF-α), cell apoptosis and
caspase-3 activity were inhibited by NSCs. In addition, Olig2 and
myelin basic protein immunohistochemy staining showed that prenatal NSCs
transplantation augmented the myelination in the periventricular white matter of offspring. In conclusion, we think that prenatal therapeutic strategies, such as in utero NSCs
transplantation, may prevent prenatal white matter injury after birth.