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BioMed Research International
Volume 2014 (2014), Article ID 721968, 13 pages
http://dx.doi.org/10.1155/2014/721968
Research Article

Vascular Endothelial Growth Factor Increases during Blood-Brain Barrier-Enhanced Permeability Caused by Phoneutria nigriventer Spider Venom

1Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil
2Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil
3Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), 31270-901 Belo Horizonte, MG, Brazil

Received 25 May 2014; Revised 26 July 2014; Accepted 5 August 2014; Published 27 August 2014

Academic Editor: Yoshinori Marunaka

Copyright © 2014 Monique C. P. Mendonça et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Phoneutria nigriventer spider accidental envenomation provokes neurotoxic manifestations, which when critical, results in epileptic-like episodes. In rats, P. nigriventer venom (PNV) causes blood-brain barrier breakdown (BBBb). The PNV-induced excitotoxicity results from disturbances on Na+, K+ and Ca2+ channels and glutamate handling. The vascular endothelial growth factor (VEGF), beyond its angiogenic effect, also, interferes on synaptic physiology by affecting the same ion channels and protects neurons from excitotoxicity. However, it is unknown whether VEGF expression is altered following PNV envenomation. We found that adult and neonates rats injected with PNV showed immediate neurotoxic manifestations which paralleled with endothelial occludin, β-catenin, and laminin downregulation indicative of BBBb. In neonate rats, VEGF, VEGF mRNA, and Flt-1 receptors, glutamate decarboxylase, and calbindin-D28k increased in Purkinje neurons, while, in adult rats, the BBBb paralleled with VEGF mRNA, Flk-1, and calbindin-D28k increases and Flt-1 decreases. Statistically, the variable age had a role in such differences, which might be due to age-related unequal maturation of blood-brain barrier (BBB) and thus differential cross-signaling among components of the glial neurovascular unit. The concurrent increases in the VEGF/Flt-1/Flk-1 system in the cerebellar neuron cells and the BBBb following PNV exposure might imply a cytokine modulation of neuronal excitability consequent to homeostatic perturbations induced by ion channels-acting PNV neuropeptides. Whether such modulation represents neuroprotection needs further investigation.