The role of brain endothelial surface charge and glycocalyx in the function and integrity of the blood-brain barrier

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.

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The Role of Autophagy during Group BStreptococcusInfection of Blood-Brain Barrier Endothelium

Journal of Biological Chemistry ◽

10.1074/jbc.m114.588657 ◽

2014 ◽

Vol 289 (52) ◽

pp. 35711-35723 ◽

Cited By ~ 31

Author(s):

Andrew S. Cutting ◽

Yvette Del Rosario ◽

Rong Mu ◽

Anthony Rodriguez ◽

Andreas Till ◽

...

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Blood Brain

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Role of thrombin-PAR1-PKCθ/δ axis in brain pericytes in thrombin-induced MMP-9 production and blood–brain barrier dysfunction in vitro

Neuroscience ◽

10.1016/j.neuroscience.2017.03.026 ◽

2017 ◽

Vol 350 ◽

pp. 146-157 ◽

Cited By ~ 28

Author(s):

Takashi Machida ◽

Shinya Dohgu ◽

Fuyuko Takata ◽

Junichi Matsumoto ◽

Ikuya Kimura ◽

...

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain ◽

Brain Pericytes

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