The effects of blood–brain barrier disruption on glial cell function in multiple sclerosis

2009 ◽  
Vol 37 (1) ◽  
pp. 329-331 ◽  
Author(s):  
Stephen McQuaid ◽  
Paula Cunnea ◽  
Jill McMahon ◽  
Una Fitzgerald
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Blood Brain Barrier ◽  
Cell Function ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Normal Appearing White Matter ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
Brain Barrier Disruption

Dysfunction of the BBB (blood–brain barrier) is a major hallmark of MS (multiple sclerosis). Studies in our laboratories over the last decade have shown that increased BBB permeability is associated with decreased expression of TJ (tight junction) proteins in brain capillary endothelial cells. Results have revealed that TJ abnormalities were most common in active lesions (42% of vessels affected), but were also present in inactive lesions (23%) and in MS normal-appearing white matter (13%). Importantly, TJ abnormality was also positively associated with leakage of the serum protein fibrinogen which has recently been shown to be an activator of microglia. TJ abnormality and the resultant vascular permeability in both lesional and non-lesional white matter may impair tissue homoeostasis, which may have effects on disease progression, repair mechanisms and drug delivery.

Quantification of subtle blood-brain barrier disruption in non-enhancing lesions in multiple sclerosis: a study of disease and lesion subtypes

2007 ◽  
Vol 13 (7) ◽  
pp. 884-894 ◽  
Author(s):  
D. Soon ◽  
DJ Tozer ◽  
DR Altmann ◽  
PS Tofts ◽  
DH Miller
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Cross Sectional ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Normal Ranges ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Brain Barrier Disruption

Few attempts have been made to detect subtle blood-brain barrier (BBB) leakage in visibly non-enhancing MRI lesions in multiple sclerosis (MS). For 19 patients, longitudinal relaxation time (T1) maps were generated from MRI scans obtained before, and at 20, 40 and 60 minutes after injection of gadolinium (Gd)-DTPA (0.3 mmol/kg). Regions of interest (ROI) were placed around non-enhancing lesions, and in paired contralateral normal appearing brain tissue (NABT). Post-Gd rate of R1 (=1/T1) rise (ΔR1/Δt), was used to quantify leakage. ΔR1/Δt was greater in lesions than paired NABT ( P ≤ 0.001 at all post-Gd timepoints). ΔR1/Δt was greater in T1 hypointense than isointense lesions ( P = 0.001 and 0.01 for first and second timepoints respectively), and negatively related to lesion cross sectional area ( P ≤ 0.001 at all post-Gd timepoints). Relapsing remitting (RRMS) lesions had a greater initial ΔR1/Δt than secondary progressive (SPMS) lesions ( P = 0.04), but this was not seen in subsequent timepoints. ΔR1/Δt in visibly enhancing lesions was significantly greater than in visibly non-enhancing lesions, with no overlap in the normal ranges of the two populations. Subtle BBB leakage is a consistent feature in non-enhancing lesions, and is distinct from the overt BBB leakage observed in visibly enhancing lesions. It is detectable using quantitative contrast-enhanced MRI. It is apparent in all clinical and lesion subtypes studied, and greater in T1 hypointense and smaller lesions. Larger initial ΔR1/Δt in RRMS than SPMS lesions may reflect differences in blood volume rather than BBB leakage. Multiple Sclerosis 2007; 13: 884—894. http://msj.sagepub.com

Quantitative contrast-enhanced magnetic resonance imaging to evaluate blood-brain barrier integrity in multiple sclerosis: a preliminary study

2001 ◽  
Vol 7 (2) ◽  
pp. 75-82 ◽  
Author(s):  
N C Silver ◽  
P S Tofts ◽  
M R Symms ◽  
G J Barker ◽  
A J Thompson ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
White Matter ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Resonance Imaging ◽  
Post Contrast ◽  
Time Points ◽  
Normal Appearing White Matter ◽  
Blood Brain

Gadolinium enhanced magnetic resonance imaging detects focal blood-brain barrier breakdown in new inflammatory multiple sclerosis lesions, but such lesions do not correlate with disease progression. To explore whether the latter might relate to subtle but widespread blood-brain barrier (BBB) breakdown with low grade inflammation mediating tissue damage, quantitative techniques were used to detect subtle gadolinium enhancement within otherwise normal-appearing white matter and within lesions not showing visible enhancement. T1-weighted imaging was performed prior to and at 5, 20 and 40 min following injection of 0.3 mmol/kg gadopentate dimeglumine in 33 patients with multiple sclerosis and five healthy control subjects. In healthy controls, a significant increase in white matter signal 5 min following contrast injection was observed (1.8%, P < 0.0005); the signal returned to baseline values by 20 min. In multiple sclerosis patients, a non-significant trend was noted for signal to remain elevated in normal-appearing white matter at the 20 and 40 min post-contrast time points; this was most apparent in primary progressive multiple sclerosis. Significant increases in signal intensity were noted at all time points post contrast in apparent non-enhancing lesions. The transient post contrast signal increase in controls is likely due to intravascular gadopentate dimeglumine. The persistent increases in signal intensity in non-enhancing lesions suggest more widespread abnormalities in BBB than is visually apparent, but substantiation of BBB leakage in normal appearing white matter will require further study using more sensitive methods.

scholarly journals Fingolimod Prevents Blood-Brain Barrier Disruption Induced by the Sera from Patients with Multiple Sclerosis

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0121488 ◽  
Author(s):  
Hideaki Nishihara ◽  
Fumitaka Shimizu ◽  
Yasuteru Sano ◽  
Yukio Takeshita ◽  
Toshihiko Maeda ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption
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