Vascular endothelial growth factor attenuates status epilepticus-induced behavioral impairments in rats

Abstract

Vascular endothelial growth factor (VEGF) is a vascular growth factor more recently recognized as a neurotrophic factor (for review see 1). We previously reported that endogenous VEGF protein is dramatically upregulated after pilocarpine-induced status epilepticus in the rat, and that intra-hippocampal infusions of recombinant human VEGF significantly protected against the loss of hippocampal CA1 neurons in this model2. We hypothesized that we would see a preservation of cognitive and emotional functioning with VEGF treatment accompanying the neuroprotection previously observed in this paradigm. Using the Morris water maze to evaluate learning and memory, and the light-dark task to assess anxiety, we found a selective profile of preservation. Specifically, VEGF completely preserved normal anxiety functioning and partially but significantly protected learning and memory after status epilepticus. To determine whether VEGF’s ability to attenuate behavioral deficits was accompanied by sustained preservation of hippocampal neurons, we stereologically estimated CA1 pyramidal neuron densities at four weeks after status epilepticus. At this time point, we found no significant difference in neuronal densities between VEGF- and control-treated status epilepticus animals, suggesting that VEGF could have protected hippocampal functioning independent of its neuroprotective effect.

Transplantation of Bone Marrow Mononuclear Cells Modulates Hippocampal Expression of Growth Factors in Chronically Epileptic Animals

“…Neuronal and glial cells regulate the VEGF expression after seizures in the rodent hippocampus, suggesting a neuroprotective role of VEGF in epilepsy . Besides, VEGF has also been found to significantly protect learning and memory after SE . Our findings that epileptic tissues promote a significant increase in VEGF production in response to BMMCs suggest that this mechanism could contribute to the cognitive preservation we observed in previous studies using BMMC transplantation in epilepsy.…”

“…A large array of growth factors has control upon cell survival, proliferation, and differentiation in the central nervous system . In our study, we focused on BDNF, NGF, GDNF, VEGF, and TGF‐ β 1 because several reports in the literature suggest that these factors are involved in epileptogenic processes . Here, we showed that BDNF protein was increased 14 days posttransplantation, and BDNF mRNA and TrkB mRNA receptor expressions were increased 7 days posttransplantation in relation to saline‐treated epileptic animals.…”

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain

“…The relationship between adult neurogenesis and the NVU has been studied (Goldman and Chen, 2011), and a recent study reported that microvascular hemodynamics modulate adult neurogenesis (Shen et al, 2019). Furthermore, VEGF administration suppressed neuronal loss in the hippocampal CA1 region 24 h but not one month after pilocarpine-induced SE in rats (Nicoletti et al, 2010). Additionally, when rats were treated with VEGF and angiopoietin-1, VEGF-induced vascular permeability was suppressed without affecting neuroprotective effects of VEGF (Nicoletti et al, 2008).…”

Increased Placental Growth Factor in Cerebrospinal Fluid of Patients with Epilepsy

“…VEGF has also been recognized as a neurotrophic factor [27,28], which could potentially protect vulnerable cells from seizures related damage [26]. VEGF induced significant preservation of hippocampal neurons after SE [4], completely preserved normal anxiety functioning, and partially but significantly protected learning and memory in the rat after pilocarpine-induced SE [29].…”