Neural stem cell changes and spatial distribution of AQP4 expression in a fetal goat model of obstructive hydrocephalus

Abstract

Background

Fetal ventriculomegaly (VM) is a common congenital abnormality with poor outcomes in severe cases, the mechanisms of which include cerebrospinal fluid（CSF）circulation disorders and abnormal neural development. While Aquaporin 4 (AQP4) plays an important role in CSF circulation, its expression in fetal VM has not been fully studied.

Methods

Fetal goats at 90–100 days of gestation were divided into experimental (hydrocephalus induced by BioGlue ® injection) and control (untreated cotwin) groups. Ventricular changes were monitored using ultrasound and magnetic resonance imaging (MRI). Brain tissues from the periventricular area, subventricular zone, and corpus callosum were collected for immunofluorescence staining to observe neural stem cells, microglia, and astrocytes. AQP4 expression was analyzed by immunofluorescence, western blotting, and real-time quantitative polymerase chain reaction.

Results

The ventricles of hydrocephalic goats were significantly enlarged (> mean + 2 SDs) compared with controls. The number of proliferating neural stem cells in the subventricular zone decreased significantly (P < 0.01). Microglial and astrocyte numbers increased significantly in the hydrocephalus group (P < 0.01). AQP4 expression was higher in the corpus callosum, periventricular, and subventricular zones (P < 0.01), with the largest increase in the subventricular zone. AQP4 expression correlated with the increase in IBA1-positive cells (r = 0.979, P = 0.004; r = 0.991, P < 0.001).

Conclusion

This study revealed pathological changes following fetal VM as well as the spatial expression of AQP4. These findings provide insights into the pathological changes associated with fetal VM and identify potential therapeutic targets.