The protective effects of bioactive (RS)-glucoraphanin on the permeability of the mice blood-brain barrier following experimental autoimmune encephalomyelitis.
OBJECTIVE
Alterations in blood-brain barrier (BBB) permeability are due to the disruption of the Tight Junctions (TJs), large multiprotein complexes important for the maintenance of structural integrity and for permeability of the barrier. In this experimental study we evaluated the neuroprotective role of (RS)-glucoraphanin, a glucosinolate present in Brassicaceae, notably in Tuscan black kale, and bioactivated with myrosinase enzyme (bioactive RS-GRA) (10 mg/kg/d intraperitoneally), to prevent the dysfunction of BBB, in an experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS).


METHODS
EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55 in mice. By western blot analysis of brain tissues, we evaluated expression and distribution of the TJ-associated proteins, claudin-1, -3, -5 and ZO-1. Additionally, in order to gain a better insight into the mechanisms of action of bioactive RS-GRA, we investigated Foxp3, ERK1/2 and caspase 3 expression associated both to inflammatory response as well as to apoptotic pathway.


RESULTS
Our results demonstrated that treatment with bioactive RS-GRA counteracts the alteration of all these parameters and preserves TJ integrity through an antinflammatory and antiapoptotic activity during MS.


CONCLUSIONS
Bioactive RS-GRA, could be a therapeutic perspective helpful in preventing dysfunction of the BBB.
IRCCS Centro Neurolesi "Bonino-Pulejo", Contrada Casazza, Messina, Italy. emazzon.irccs@gmail.com.
S
S
Giacoppo
M
M
Galuppo
R
R
Iori
G R
GR
De Nicola
P
P
Bramanti
E
E
Mazzon
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000196:embryology*; D053148:Caspase 3 / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism; D062465:Claudin-3 / Q000378:metabolism; D062507:Claudin-5 / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005961:Glucosinolates / Q000494:pharmacology*; D007096:Imidoesters / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010091:Oximes; D010539:Permeability / Q000187:drug effects*; D013454:Sulfoxides; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D062445:Claudin-1; D062465:Claudin-3; D062507:Claudin-5; C568113:Cldn1 protein, mouse; C491511:Cldn5 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D005961:Glucosinolates; D007096:Imidoesters; D018696:Neuroprotective Agents; D010091:Oximes; D013454:Sulfoxides; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D053148:Caspase 3; C119494:glucoraphanin