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Blood–brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons
Author(s) -
Rite Inmaculada,
Machado Alberto,
Cano Josefina,
Venero José L.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04567.x
Subject(s) - dopaminergic , substantia nigra , tyrosine hydroxylase , mptp , neuroscience , population , vascular endothelial growth factor , biology , chemistry , dopamine , medicine , cancer research , vegf receptors , environmental health
Abstract We have evaluated the possibility that changes in the vascular system may constitute a contributing factor for the death of nigral dopaminergic neurons in Parkinson’s disease. Thus, we have employed intranigral injections of vascular endothelial growth factor (VEGF), the most potent inducer of blood–brain barrier (BBB) permeability. A single dose of 1 μg of VEGF, chosen from a dose‐response study, highly disrupted the BBB in the ventral mesencephalon in a time‐dependent manner. A strong regional correlation between BBB disruption and loss of tyrosine hydroxylase‐positive neurons was evident. Moreover, Fluoro‐Jade B labelling showed the presence of dying neurons in the substantia nigra in response to VEGF injection. High number of TUNEL‐positive nuclei was observed in this area along with activation of caspase 3 within nigral dopaminergic neurons. Analysis of the glial population demonstrated a strong inflammatory response and activation of astroglia in response to BBB disruption. We conclude that disruption of the BBB may be a causative factor for degeneration of nigral dopaminergic neurons.