Human umbilical cord mesenchymal stem cells alleviate brain injury and promote neuroregeneration via BDNF/TrkB/CREB/PI3K-Akt pathway in preterm rats with intraventricular hemorrhage.

OBJECTIVE

To explore the neuroprotective effect and molecular mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) in preterm rats with intraventricular hemorrhage (IVH), and provide experimental basis for clinical treatment of neonatal IVH.

METHODS

Tissue block adherence method was used to isolate and culture hUC-MSCs, and P4 Sprague-Dawley premature rats were divided into sham, IVH model, and hUC-MSC treatment groups. Collagenase VIIS was injected to establish IVH model, and hUC-MSCs were injected into lateral ventricles. Cell colonization, body weight, neurobehavior, brain histology, apoptosis, and related molecular indicators were detected via fluorescence tracking, behavioral tests, staining, RT-PCR, Western blot (WB), and ELISA. Bioinformatics combined with ANA12 blocking assay verified core pathways.

RESULTS

hUC-MSCs survived in rat brain for at least 7 days. Compared with the model group, the treatment group gained weight faster, neurobehavioral function was markedly improved, neuronal apoptosis decreased sharply, and brain tissue damage was alleviated. hUC-MSCs up-regulated anti-apoptotic, anti-inflammatory, antioxidant and neurogenesis-related molecules and activated BDNF/TrkB/CREB/PI3K-Akt pathway; TrkB blockade reversed all protective effects.

CONCLUSION

hUC-MSCs exert multi-target neuroprotection by activating BDNF/TrkB/CREB/PI3K-Akt pathway, which offers a novel strategy for IVH treatment in preterm infants.