scholarly journals Gadolinium enhancement of cranial nerves: Implications for interstitial fluid drainage from brainstem into cranial nerves in humans

2021 ◽  
Vol 118 (45) ◽  
pp. e2106331118
Author(s):  
Aravinthan Varatharaj ◽  
Roxana O. Carare ◽  
Roy O. Weller ◽  
Mary Gawne-Cain ◽  
Ian Galea
Keyword(s):  
Multiple Sclerosis ◽  
High Resolution ◽  
Interstitial Fluid ◽  
Cranial Nerves ◽  
Gadolinium Enhancement ◽  
Brainstem Lesion ◽  
Blood Brain Barrier Disruption ◽  
High Resolution Mri ◽  
Brain Barrier Disruption ◽  
Oculomotor Nerves

Drainage of interstitial fluid and solutes from the brainstem has not been well studied. To map one drainage pathway in the human brainstem, we took advantage of the focal blood–brain barrier disruption occurring in a multiple sclerosis brainstem lesion, coupled with intravenous injection of gadolinium, which simulates an intraparenchymal injection of gadolinium tracer within the restricted confines of this small brain region. Using high-resolution MRI, we show how it is possible for interstitial fluid to drain into the adjacent trigeminal and oculomotor nerves, in keeping with a pathway of communication between the extracellular spaces of the brainstem and cranial nerve parenchyma.

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.

Alterations in serum MMP-8, MMP-9, IL-12p40 and IL-23 in multiple sclerosis patients treated with interferon-β1b

2010 ◽  
Vol 16 (7) ◽  
pp. 801-809 ◽  
Author(s):  
JS Alexander ◽  
MK Harris ◽  
SR Wells ◽  
G. Mills ◽  
K. Chalamidas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Magnetic Resonance Imaging ◽  
First Year ◽  
Serial Measurement ◽  
Blood Brain Barrier Disruption ◽  
Matrix Metalloproteinase 1 ◽  
Relapsing Remitting ◽  
Th17 Cytokines ◽  
Brain Barrier Disruption ◽  
Multiple Sclerosis Patients

Background: Interferon-β1b (IFN-β1b), an effective treatment for multiple sclerosis (MS), lessens disease severity in MS patients. However, the mechanisms of its immunoregulatory and anti-inflammatory effects in MS remain only partially understood. Matrix metalloproteinases (MMP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are involved in blood brain barrier disruption and formation of MS lesions. Th1/Th17 cytokines e.g. interleukins IL-12p40, IL-17, and IL-23, are associated with MS disease activity and are significant players in pathogenesis of MS. Objective: During a 1-year prospective study, we serially measured serum MMP-8, MMP-9, TIMP-1, IL-12p40, IL-17, and IL-23 in 24 patients with relapsing—remitting MS. We compared the results to clinical course and to brain magnetic resonance imaging. IFN-β1b decreased serum MMP-8 and MMP-9 (not TIMP-1). Results: The sustained treatment with IFN-β1b attenuated the pro-inflammatory environment by significantly reducing the serum IL-12p40, IL-23, and showed a trend for decreasing IL-17. Decreased serum MMP-8, MMP-9, IL-12 and IL-23 levels were correlated with a decrease in the number of contrast-enhanced T2-weighted lesions. Conclusion: Early treatment of MS with IFN-β1b may stabilize clinical disease by attenuating levels of inflammatory cytokines and MMPs. Serial measurement of inflammatory mediators may serve as sensitive markers to gauge therapeutic responses to IFN-β1b during the first year of treatment.

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

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