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Updated: Apr 16, 2026
Neonatal Subventricular Zone Electroporation
Published on: February 11, 2013
Intrauterine Growth Restriction: Effects on Neural Precursor Cell Proliferation and Angiogenesis in the Foetal
Mary Tolcos1, Rachel Markwick, Rachael O'Dowd
1Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Vic., Australia.
Insights
Chronic placental insufficiency in guinea pigs affects fetal brain development. This study reveals a link between blood vessel growth and neural precursor cell proliferation in the fetal subventricular zone.
Area of Science:
- Neuroscience
- Developmental Biology
- Perinatal Medicine
Background:
- Adverse prenatal factors can disrupt fetal brain development, leading to neurological disorders.
- Intrauterine insults during critical developmental periods like neurogenesis and gliogenesis are implicated in abnormal brain formation.
Purpose of the Study:
- To investigate the impact of chronic placental insufficiency (CPI) on cell proliferation and the microenvironment within the fetal subventricular zone (SVZ).
- To explore the relationship between angiogenesis and neurogenesis in the developing fetal brain.
Main Methods:
- CPI was induced in pregnant guinea pigs via unilateral uterine artery ligation, creating growth-restricted (GR) fetuses.
- Fetal brains at 60 days of gestation were analyzed using immunohistochemistry for proliferating cells (Ki67), immature neurons, astrocytes, microglia (Iba-1), and microvasculature (von Willebrand factor) in the SVZ.
- Regression analysis was used to correlate various markers with brain weight and with each other.
Main Results:
- No significant overall difference in Ki67-positive cells, blood vessel percentage, or microglia density between control and GR fetuses.
- Negative correlation found between Ki67-positive cells, blood vessel percentage in the ventral SVZ, and fetal brain weight.
- Positive correlation observed between blood vessel density and the number of proliferating cells (Ki67-IR) in the SVZ.
Conclusions:
- Demonstrated an association between angiogenesis and neurogenesis in the fetal neurogenic niche (SVZ).
- Identified a potential therapeutic window for administering trophic support to promote neuroregeneration in growth-restricted fetuses.
Abstract:
Exposure to adverse prenatal factors can result in abnormal brain development, contributing to the aetiology of several neurological disorders. Intrauterine insults could occur during neurogenesis and gliogenesis, disrupting these events. Here we investigate the effects of chronic placental insufficiency (CPI) on cell proliferation and the microenvironment in the subventricular zone (SVZ). At 30 days of gestation (DG; term ∼67 DG), CPI was induced in pregnant guinea pigs via unilateral uterine artery ligation to produce growth-restricted (GR) foetuses (n = 7); controls (n = 6) were from the unoperated horn. At 60 DG, foetal brains were stained immunohistochemically to identify proliferating cells (Ki67), immature neurons (polysialylated neuronal cell adhesion molecule), astrocytes (glial fibrillary acidic protein), microglia (ionised calcium-binding adaptor molecule-1, Iba-1) and the microvasculature (von Willebrand factor) in the SVZ. There was no overall difference (p > 0.05) in the total number of Ki67-immunoreactive (IR) cells, the percentage of SVZ occupied by blood vessels or the density of Iba-1-IR microglia in control versus GR foetuses. However, regression analysis across both groups revealed that both the number of Ki67-IR cells and the percentage of SVZ occupied by blood vessels in the ventral SVZ were negatively correlated (p < 0.05) with brain weight. Furthermore, in the SVZ (dorsal and ventral) the density of blood vessels positively correlated (p < 0.05) with the number of Ki67-IR cells. Double-labelling immunofluorescence suggested that the majority of proliferating cells were likely to be neural precursor cells. Thus, we have demonstrated an association between angiogenesis and neurogenesis in the foetal neurogenic niche and have identified a window of opportunity for the administration of trophic support to enhance a neuroregenerative response.
