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.

hUC-MSCs survived and colonized in rat brain tissue for at least 7 days after injection into lateral ventricles.

• Fluorescence tracking was used to monitor cell colonization in vivo.
• Cells were injected directly into lateral ventricles of preterm rats with IVH.
• Cell survival was confirmed over the 7-day observation period.
• P4 Sprague-Dawley premature rats were used as the animal model.

hUC-MSC treatment resulted in faster body weight gain in IVH-model rats compared to the untreated model group.

• Body weight was monitored as a general health indicator across sham, IVH model, and hUC-MSC treatment groups.
• The treatment group gained weight faster than the model group.
• Weight gain was used as one of several outcome measures alongside neurobehavioral and histological assessments.

hUC-MSC treatment markedly improved neurobehavioral function in preterm rats with IVH compared to the model group.

• Neurobehavioral function was assessed using behavioral tests.
• The treatment group showed marked improvement compared to the IVH model group.
• Three groups were compared: sham, IVH model, and hUC-MSC treatment.

Neuronal apoptosis decreased sharply in hUC-MSC-treated rats compared to the IVH model group.

• Apoptosis was detected using staining methods.
• The paper describes the decrease as 'sharp' relative to the model group.
• Anti-apoptotic molecules were upregulated in the treatment group.
• Brain tissue damage was also alleviated in the treatment group.

hUC-MSCs upregulated anti-apoptotic, anti-inflammatory, antioxidant, and neurogenesis-related molecules in IVH rats.

• Molecular indicators were detected via RT-PCR, Western blot, and ELISA.
• Multiple molecular categories were affected: anti-apoptotic, anti-inflammatory, antioxidant, and neurogenesis-related.
• This multi-target effect suggests broad neuroprotective activity.
• These changes were observed in comparison to the untreated IVH model group.

hUC-MSCs activated the BDNF/TrkB/CREB/PI3K-Akt signaling pathway in preterm rats with IVH.

• Pathway activation was identified through bioinformatics analysis combined with molecular assays.
• Western blot and RT-PCR were used to confirm pathway component expression.
• The pathway was identified as the core molecular mechanism underlying neuroprotection.
• BDNF (brain-derived neurotrophic factor) and its receptor TrkB were key upstream components.

Pharmacological blockade of TrkB with ANA12 reversed all protective effects of hUC-MSCs, confirming the centrality of the BDNF/TrkB pathway.

• ANA12 is a selective TrkB antagonist used to block TrkB signaling.
• A blocking assay was combined with bioinformatics analysis to verify the core pathway.
• All protective effects observed with hUC-MSC treatment were reversed upon TrkB blockade.
• This finding confirms that hUC-MSC neuroprotection is dependent on TrkB receptor signaling.

The IVH model was established in P4 Sprague-Dawley premature rats using collagenase VIIS injection into the brain.

• Collagenase VIIS was injected to induce intraventricular hemorrhage.
• Postnatal day 4 (P4) Sprague-Dawley rats were used to model preterm brain development.
• Three experimental groups were used: sham, IVH model, and hUC-MSC treatment.
• hUC-MSCs were isolated using the tissue block adherence method and used at passage 4 (P4).

Brain histology confirmed alleviation of brain tissue damage in hUC-MSC-treated IVH rats.

• Histological assessment was performed using staining techniques.
• Brain tissue damage was evaluated and compared across sham, IVH model, and treatment groups.
• Histological findings were consistent with the neurobehavioral and molecular outcomes.