Embryonic intraventricular transplantation of neural stem cells augments inflammation-induced prenatal brain injury

Abstract

Objective: Prenatal brain injury results from undesirable circumstances during the embryonic development. Current endeavors for treating this complication are basically excluded to postnatal therapeutic approaches. Neural stem cell therapy has shown great promise for treating neurodevelopmental disorders. To our knowledge, this is the first study that investigates the therapeutic effect of in utero transplantation of neural stem cells (NSCs) in inflammation model of prenatal brain injury.

Methods: To induce prenatal injury, time-mated C57BL6J mice were intraperitoneally injected with 50 μg/kg lipopolysaccharide (LPS(on the day 15 of gestation. In the treatment group, NSCs were transplanted into the lateral ventricle of embryos on day 17 of gestation. The expression of GFAP, Iba-1, Olig2, and NeuN were assessed by real time PCR and immunohistochemistry. Changes in IL-6, TNF-α and IL-10 cytokines level, and caspase 3 activity were evaluated in the cortex of pups.

Results: Intrauterine transplanted NSCs homed to the brain cortex of offspring. Brain levels of pro-inflammatory cytokines showed a significant downward trend in the NSCs group. Furthermore, NSCs ameliorated inflammation-induced reactive microgliosis and astrogliosis as well as cellular degeneration. Apoptosis inhibition in the treated group was demonstrated by the decline in the caspase 3 activity and dark neurons.

Conclusion: This study suggests a promising prospect to initiate the treatment of prenatal brain injury before birth by intrauterine transplantation of NSCs.

Keywords: Inflammation; Intrauterine transplantation; Lipopolysaccharide; Neural stem cells; Prenatal brain injury.