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Toxins 2013, 5(12), 2572-2588; doi:10.3390/toxins5122572

Expression of VEGF and Flk-1 and Flt-1 Receptors during Blood-Brain Barrier (BBB) Impairment Following Phoneutria nigriventer Spider Venom Exposure

1
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (Unicamp) Campinas, SP 13083-887, Brazil
2
Department of Histology and Embryology, Institute of Biology, State University of Campinas (Unicamp) Campinas, SP 13083-863, Brazil
3
Cell Signaling Laboratory, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP 13081-970, Brazil
4
Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG 31270-901, Brazil
*
Author to whom correspondence should be addressed.
Received: 23 October 2013 / Revised: 30 November 2013 / Accepted: 3 December 2013 / Published: 18 December 2013
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Abstract

Apart from its angiogenic and vascular permeation activity, the vascular endothelial growth factor (VEGF) has been also reported as a potent neuronal protector. Newborn rats with low VEGF levels develop neuron degeneration, while high levels induce protective mechanisms in several neuropathological conditions. Phoneutria nigriventer spider venom (PNV) disrupts the blood-brain barrier (BBB) and causes neuroinflammation in central neurons along with excitotoxic signals in rats and humans. All these changes are transient. Herein, we examined the expression of VEGF and its receptors, Flt-1 and Flk-1 in the hippocampal neurons following envenomation by PNV. Adult and neonatal rats were evaluated at time limits of 2, 5 and 24 h. Additionally, BBB integrity was assessed by measuring the expression of occludin, β-catenin and laminin and neuron viability was evaluated by NeuN expression. VEGF, Flt-1 and Flk-1 levels increased in PNV-administered rats, concurrently with respective mRNAs. Flt-1 and Flk-1 immunolabeling was nuclear in neurons of hippocampal regions, instead of the VEGF membrane-bound typical location. These changes occurred simultaneously with the transient decreases in BBB-associated proteins and NeuN positivity. Adult rats showed more prominent expressional increases of the VEGF/Flt-1/Flk-1 system and earlier recovery of BBB-related proteins than neonates. We conclude that the reactive expressional changes seen here suggest that VEGF and receptors could have a role in the excitotoxic mechanism of PNV and that such role would be less efficient in neonate rats. View Full-Text
Keywords: hippocampus; junctional proteins; Neu-N; VEGF; VEGF receptors hippocampus; junctional proteins; Neu-N; VEGF; VEGF receptors
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Mendonça, M.C.P.; Soares, E.S.; Stávale, L.M.; Rapôso, C.; Coope, A.; Kalapothakis, E.; da Cruz-Höfling, M.A. Expression of VEGF and Flk-1 and Flt-1 Receptors during Blood-Brain Barrier (BBB) Impairment Following Phoneutria nigriventer Spider Venom Exposure. Toxins 2013, 5, 2572-2588.

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