Morphological Changes of Cortical and Hippocampal Neurons after Treatment with VEGF and Bevacizumab

Vascular endothelial growth factor (VEGF) is a hallmark of glioblastoma multiforme (GBM) and plays an important role in brain development and function. Recently, it has been reported that treatment of GBM patients with bevacizumab, an anti-VEGF antibody, may cause a decline in neurocognitive function and compromise quality of life. Therefore, we investigated the effects of VEGF and bevacizumab on the morphology and on survival of neurons and glial cells.

Dissociated cortical and hippocampal cell cultures of juvenile rats were treated with VEGF, bevacizumab, and VEGF + bevacizumab. Neuronal and glial cell viability was analyzed, and the morphology of neurons was objectified by morphometric analysis.

In cortical cultures, bevacizumab significantly decreased the number of neurons after 20 days and the number of glial cells subsequent 30 days. Additionally, an increase in the dendritic length of cortical neurons was obvious after 10 days of incubation with bevacizumab, but returned to control level after 30 days. In hippocampal cultures, cell viability was not affected by bevacizumab; however, dendritic length increased at day 10, but decreased after long-term treatment.

Therefore, bevacizumab obviously has a cytotoxic effect in cortical cultures and decreases the dendritic length in hippocampal neurons after long-term treatment.