Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury.
The integrity of the blood-brain barrier (BBB) is critical for normal brain function, and its compromise contributes to the pathophysiology of a number of CNS diseases and injuries. Using a rodent model of brain injury, the present study examines the pathophysiology of BBB disruption. Western blot and immunohistochemical analyses indicate that brain injury causes a loss of capillary endothelial cells and tight junction proteins, two critical components of the BBB. Activation of the transcription factor NF-E2-related factor-2 (Nrf2) by sulforaphane, a naturally occurring compound present in high levels in cruciferous vegetables, significantly increased the expression of endogenous cytoprotective genes in brain tissue and microvessels as indicated by real-time PCR analysis. Postinjury administration of sulforaphane reduced the loss of endothelial cell markers and tight junction proteins and preserved BBB function. These protective effects were dependent on the activity of Nrf2. Injured rats pretreated with decoy oligonucleotides containing the binding site of Nrf2, and mice lacking the nrf2 gene, did not benefit from sulforaphane administration. These findings indicate a potential therapeutic usefulness for Nrf2-activating molecules to improve the function of the neurovascular unit after injury.
Zhao
Jing
J
The Vivian L. Smith Center for Neurologic Research and Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
Moore
Anthony N
AN
Redell
John B
JB
Dash
Pramod K
PK
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000502:physiology*; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology
D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C495637:Nfe2l2 protein, rat; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane