Cerebrospinal Fluid Analysis of Pericytic Mediators in Clinically Isolated Syndrome and Multiple Sclerosis: A Preliminary Study
Abstract
DOI: 10.26650/experimed.2018.434227
Objectives: In many studies, blood brain
barrier has been shown to be compromised in multiple sclerosis patients.
Pericytes play an active role in ensuring the continuity of the blood brain
barrier along with a series of cells. In this study, the effect of pericytic
dysfunction on the development of demyelinating plaques in patients with
multiple sclerosis was investigated.
Material and Method: Concentrations of
pericyte dysfunction mediators (PDGFbb, MMP9, TIMP3 and ADAM17) in
cerebrospinal fluid of patients with clinically isolated syndrome (CIS),
relapsing remitting multiple sclerosis (RRMS) and healthy control group were
measured by ELISA and oligoclonal bands (OCB) were investigated. We aimed to
determine whether the concentration of these mediators differed between groups
and whether they correlated with lesion load, number of attacks, and EDSS
scores.
Results: Concentrations of all four
mediators were similar in patients with CIS and RRMS. However, both groups were
found to be higher than the healthy group. In the CIS and RRMS groups, the
levels of the mediators were not correlated with any parameters examined.
However, the levels of PDGFbb (p=0.045), MMP9 (p=0.037), and TIMP3 (p=0.033)
were higher in OCB positive patients than in those without OCB, whereas ADAM17
levels remained unchanged.
Conclusion: This study shows that pericytes
may play a role in the pathogenesis of MS from early stages of the disease. The
presence of higher levels in patients with OCB suggests that pericyte
dysfunction may be associated with OCB formation.
Keywords
clinically isolated syndrome pericyte cerebrospinal fluid neuroinflammation Multiple sclerosis
References
- Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler 2003;9:540-549.
- Hill J, Rom S, Ramirez SH, Persidsky Y. Emerging roles of pericytes in the regulation of the neurovascular unit in health and disease. J Neuroimmune Pharmacol 2014;9:591-605.
- Niu F, Yao H, Liao K, Buch S. HIV Tat 101-mediated loss of pericytes at the blood-brain barrier involves PDGF-BB. Ther Targets Neurol Dis 2015;2.
- Shukla V, Shakya AK, Shukla M, Kumari N, Krishnani N, Dhole TN, Misra UK. Circulating levels of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases during Japanese encephalitis virus infection. Virusdisease 2016;27:63-76.
- Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 2009;158:983-994.
- Muramatsu R, Kuroda M, Matoba K, Lin H, Takahashi C, Koyama Y, Yamashita T. Prostacyclin prevents pericyte loss and demyelination induced by lysophosphatidylcholine in the central nervous system. The Journal of biological chemistry 2015;290:11515-11525.
- Fainardi E, Castellazzi M, Bellini T, Manfrinato MC, Baldi E, Casetta I, Paolino E, Granieri E, Dallocchio F. Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler 2006;12:294-301.
- Gold SM, Chalifoux S, Giesser BS, Voskuhl RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. Journal of neuroinflammation 2008;5:32.
- Haddock G, Cross AK, Plumb J, Surr J, Buttle DJ, Bunning RA, Woodroofe MN. Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter. Mult Scler 2006;12:386-396.
- Ljubisavljevic S, Stojanovic I, Basic J, Vojinovic S, Stojanov D, Djordjevic G, Pavlovic D. The Role of Matrix Metalloproteinase 3 and 9 in the Pathogenesis of Acute Neuroinflammation. Implications for Disease Modifying Therapy. J Mol Neurosci 2015;56:840-847.
- Farina G, Magliozzi R, Pitteri M, Reynolds R, Rossi S, Gajofatto A, Benedetti MD, Facchiano F, Monaco S, Calabrese M. Increased cortical lesion load and intrathecal inflammation is associated with oligoclonal bands in multiple sclerosis patients: a combined CSF and MRI study. Journal of neuroinflammation 2017;14:40.
Klinik İzole Sendrom ve Multipl Skleroz Hastalarının Beyin Omurilik Sıvılarında Perisitik Mediatörlerin Analizi: Pilot Çalışma
Abstract
DOI: 10.26650/experimed.2018.434227
Amaç: Multipl skleroz’da kan beyin
bariyerinin bozulduğu pek çok çalışmada gösterilmiştir. Perisitler bir dizi
hücre yanında kan beyin bariyerinin devamlılığının sağlanmasında aktif rol
üstlenir. Bu çalışmada multipl skleroz hastalarında perisit disfonksiyonunun
demyelinizan plakların gelişimindeki etkisi araştırılmıştır.
Gereç ve Yöntem: Klinik izole sendrom
(KİS), relapsing remitting multipl skleroz (RRMS) ve sağlıklı kontrol grubundan
alınan beyin omurilik sıvılarında perisit disfonksiyon mediatörlerinin (PDGFbb,
MMP9, TIMP3 ve ADAM17) konsantrasyonları ELISA ile ölçüldü ve oligoklonal
bantlar (OKB) araştırıldı. Bu mediyatörlerin, gruplar arasındaki farklılıkları
lezyon yükü, atak sayısı ve EDSS skorları ile korelasyon gösterip göstermediği
belirlendi.
Bulgular: Her dört mediyatörün
konsantrasyonları KİS ve RRMS hastalarında benzer bulundu. Bununla beraber her
iki grupta sağlıklı kontollerden yüksek bulundu. KİS ve RRMS grubunda,
mediyatörlerin seviyelerinin bakılan hiçbir parametre ile korelasyon göstermediği
saptandı. Buna karşın, beyin omurilik sıvılarında OKB bulunan hastalarda PDGFbb
(p=0,045), MMP9 (p=0,037) ve TIMP3 (p=0,033) düzeylerinin OKB bulunmayanlara
göre daha yüksek olduğu, ADAM17 seviyelerinin ise değişmediği görüldü.
Sonuç: Bu çalışma perisit disfonksiyon
mediyatörlerinin MS’in patogenezinde hastalığın erken dönemlerinden itibaren
rol alabileceğini göstermektedir. Oligoklonal band bulunan hastalarda daha
yüksek seviyelerdeki mevcudiyeti, perisit disfonksiyonunun OKB oluşumu ile bir
ilgisi olabileceğini akla getirmektedir.
Keywords
klinik izole sendrom perisit beyin omurilik sıvısı nöroinflamasyon Multipl skleroz nöroinflamasyon
References
- Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler 2003;9:540-549.
- Hill J, Rom S, Ramirez SH, Persidsky Y. Emerging roles of pericytes in the regulation of the neurovascular unit in health and disease. J Neuroimmune Pharmacol 2014;9:591-605.
- Niu F, Yao H, Liao K, Buch S. HIV Tat 101-mediated loss of pericytes at the blood-brain barrier involves PDGF-BB. Ther Targets Neurol Dis 2015;2.
- Shukla V, Shakya AK, Shukla M, Kumari N, Krishnani N, Dhole TN, Misra UK. Circulating levels of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases during Japanese encephalitis virus infection. Virusdisease 2016;27:63-76.
- Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 2009;158:983-994.
- Muramatsu R, Kuroda M, Matoba K, Lin H, Takahashi C, Koyama Y, Yamashita T. Prostacyclin prevents pericyte loss and demyelination induced by lysophosphatidylcholine in the central nervous system. The Journal of biological chemistry 2015;290:11515-11525.
- Fainardi E, Castellazzi M, Bellini T, Manfrinato MC, Baldi E, Casetta I, Paolino E, Granieri E, Dallocchio F. Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler 2006;12:294-301.
- Gold SM, Chalifoux S, Giesser BS, Voskuhl RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. Journal of neuroinflammation 2008;5:32.
- Haddock G, Cross AK, Plumb J, Surr J, Buttle DJ, Bunning RA, Woodroofe MN. Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter. Mult Scler 2006;12:386-396.
- Ljubisavljevic S, Stojanovic I, Basic J, Vojinovic S, Stojanov D, Djordjevic G, Pavlovic D. The Role of Matrix Metalloproteinase 3 and 9 in the Pathogenesis of Acute Neuroinflammation. Implications for Disease Modifying Therapy. J Mol Neurosci 2015;56:840-847.
- Farina G, Magliozzi R, Pitteri M, Reynolds R, Rossi S, Gajofatto A, Benedetti MD, Facchiano F, Monaco S, Calabrese M. Increased cortical lesion load and intrathecal inflammation is associated with oligoclonal bands in multiple sclerosis patients: a combined CSF and MRI study. Journal of neuroinflammation 2017;14:40.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Makale |
| Authors | |
| Publication Date | April 30, 2018 |
| Published in Issue | Year 2018 Volume: 8 Issue: 1 |
