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Neonatal excitotoxicity modifies blood‐brain barrier properties increasing its susceptibility to hypertonic shock in adulthood
Author(s) -
FajardoFregoso Blanca Fabiola,
CastañedaCabral Jose Luis,
BeasZárate Carlos,
UreñaGuerrero Mónica E.
Publication year - 2020
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1002/jdn.10027
Subject(s) - excitotoxicity , endocrinology , medicine , blood–brain barrier , glutamate receptor , cerebral cortex , neuroprotection , chemistry , biology , receptor , central nervous system
Early responses to a neurological excitotoxic process include blood‐brain barrier (BBB) impairment and overexpression of vascular endothelial growth factor (VEGF), but the long‐term effects of excitotoxicity on the BBB properties remain unknown. To assess this, we induced an excitotoxic process on male rats by neonatal monosodium glutamate (MSG) treatment. At postnatal day (PD) 60, we measured the expression level of structural proteins of the BBB and the VEGF type‐2 receptor (VEGFR‐2) protein in the cerebral motor cortex (CMC), striatum (STR), hippocampus (Hp), entorhinal cortex (Ent), and hypothalamus (Hyp). We also measured BBB permeability in the same cerebral regions. Neonatal MSG treatment significantly reduced the protein expression level of claudin‐5 in the CMC, and of ZO‐1 in the CMC and Hp, and increased the expression level of plasmalemmal vesicle‐associated protein in the CMC, and of VEGFR‐2 in all regions except for the Hyp. BBB permeability was significantly higher in all studied regions of MSG‐treated animals after hypertonic shock (HS). The increased BBB permeability observed in the MSG‐treated animals after HS was reversed by VEGFR‐2 inhibition with SU5416. We conclude that neonatal excitotoxicity leads to lasting impairment on BBB properties in adulthood, increasing its susceptibility to HS that could be regulated by VEGFR‐2 activity inhibition.