Subacute treatment with vascular endothelial growth factor after traumatic brain injury increases angiogenesis and gliogenesis

Vascular endothelial growth factor (VEGF) is neuroprotective and induces neurogenesis and angiogenesis when given early after traumatic brain injury (TBI). However, the effects of VEGF administration in the subacute phase after TBI remain unknown. Mice were subjected to TBI and treated with vehicle or VEGF beginning 7 days later for an additional 7 days. The animals were injected with BrdU to label proliferating cells and examined with a motor-sensory scale at pre-determined time points. Mice were killed 90 days post injury and immunohistochemistry was used to study cell fates. Our results demonstrate that lesion volumes did not differ between the groups confirming the lack of neuroprotective effects in this paradigm. VEGF treatment led to significant increments in cell proliferation (1.9 fold increase vs. vehicle, P<0.0001) and angiogenesis in the lesioned cortex (1.7 fold increase vs. vehicle, P=0.0001) but most of the proliferating cells differentiated into glia and no mature newly-generated neurons were detected. In conclusion, VEGF induces gliogenesis and angiogenesis when given 7 days post TBI. However, treated mice had only insignificant motor improvements in this paradigm, suggesting that the bulk of the beneficial effects observed when VEGF is given early after TBI results from the neuroprotective effects.