Cerebrospinal fluid aquaporin‐4‐immunoglobulin G disrupts 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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Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice

PLoS ONE ◽

10.1371/journal.pone.0218415 ◽

2019 ◽

Vol 14 (6) ◽

pp. e0218415 ◽

Cited By ~ 6

Author(s):

Yifan Zhang ◽

Kui Xu ◽

Yuchi Liu ◽

Bernadette O. Erokwu ◽

Pan Zhao ◽

...

Keyword(s):

Blood Brain Barrier ◽

Knockout Mice ◽

Water Exchange ◽

Aquaporin 4 ◽

Brain Barrier ◽

Blood Brain

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Blood–brain barrier and blood–cerebrospinal fluid barrier in normal and pathological conditions

Brain Tumor Pathology ◽

10.1007/s10014-016-0255-7 ◽

2016 ◽

Vol 33 (2) ◽

pp. 89-96 ◽

Cited By ~ 41

Author(s):

Masaki Ueno ◽

Yoichi Chiba ◽

Ryuta Murakami ◽

Koichi Matsumoto ◽

Machi Kawauchi ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Pathological Conditions ◽

Blood Brain

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Drug delivery across the blood-brain barrier and resultant reduction of heparan sulfate in the cerebrospinal fluid in the patients with Hunter syndrome (MPS II): An integrated analysis of 25-week Japanese and Brazilian data on pabinafusp alfa (JR-141)

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2020.12.182 ◽

2021 ◽

Vol 132 (2) ◽

pp. S78

Author(s):

Torayuki Okuyama ◽

Yoshikatsu Eto ◽

Norio Sakai ◽

Kimitoshi Nakamura ◽

Roberto Giugliani ◽

...

Keyword(s):

Drug Delivery ◽

Cerebrospinal Fluid ◽

Heparan Sulfate ◽

Blood Brain Barrier ◽

Hunter Syndrome ◽

Brain Barrier ◽

Integrated Analysis ◽

Mps Ii ◽

Blood Brain

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ELEVATION OF MATRIX METALLOPROTEINASES 3 AND 9 IN CEREBROSPINAL FLUID AND BLOOD IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY

Neurosurgery ◽

10.1227/01.neu.0000351768.11363.48 ◽

2009 ◽

Vol 65 (4) ◽

pp. 702-708 ◽

Cited By ~ 95

Author(s):

Mark Grossetete ◽

Jeremy Phelps ◽

Leopold Arko ◽

Howard Yonas ◽

Gary A. Rosenberg

Keyword(s):

Traumatic Brain Injury ◽

Cerebrospinal Fluid ◽

Brain Injury ◽

Matrix Metalloproteinases ◽

Blood Brain Barrier ◽

Normal Pressure Hydrocephalus ◽

Normal Pressure ◽

Brain Barrier ◽

Western Immunoblot ◽

Blood Brain

Abstract OBJECTIVE Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBI patients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P < 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION We show that MMPs are increased in the CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBI patients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.

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The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Nutrients ◽

10.3390/nu13061833 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1833

Author(s):

Shannon Morgan McCabe ◽

Ningning Zhao

Keyword(s):

Cerebrospinal Fluid ◽

Blood Brain Barrier ◽

Blood Circulation ◽

Critical Role ◽

Systemic Circulation ◽

Brain Parenchyma ◽

Brain Barrier ◽

Blood Brain ◽

The Brain

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.

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Association Between Vancomycin Blood Brain Barrier Penetration and Clinical Response in Postsurgical Meningitis

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3493f ◽

2017 ◽

Vol 20 ◽

pp. 161 ◽

Cited By ~ 1

Author(s):

Qing Wang ◽

Si Chen ◽

Yan-Gang Zhou ◽

Ping Xu ◽

Yi-Ping Liu ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Clinical Response ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Serum Samples ◽

Cell Counts ◽

Blood Cell Counts ◽

Blood Brain ◽

Barrier Penetration ◽

White Blood Cell Counts

PURPOSE: This study investigated the association between vancomycin blood brain barrier penetration and clinical response in patients with postsurgical meningitis. METHODS: Adult patients with postsurgical meningitis were recruited. Eligible patients received vancomycin 500 mg every 6 h for at least 5 days. On day 3 or 4, cerebrospinal fluid (CSF) and simultaneous serum samples were obtained to determine CSF minimum concentrations (Cmin), serum Cmin and CSF to serum Cmin ratio. RESULTS: Twenty-two patients (14 men and 8 women; mean age of 52.6± 12.1 years) were recruited. The vancomycin Cmin was 3.63 ± 1.64 mg/L in CSF and 13.38 ± 5.36 mg/L in serum, with the CSF to serum Cmin ratio of 0.291 ± 0.118. The Cmin in serum and in CSF showed a significant correlation (p=0.005, r =0.575). The vancomycin CSF Cmin had a significant correlation with the decline of white blood cell counts (WBCs) in CSF (p=0.003, r =0.609). CSF Cmin, serum Cmin and CSF to serum Cmin ratio all showed no significant correlation with clinical response (p=0.335, 0.100, 0.679, respectively). CONCLUSIONS: There was a positive correlation between serum Cmin and CSF Cmin. However, only CSF Cmin is positively correlated with WBCs improvement in CSF. All other parameters such as serum Cmin, CSF Cmin and CSF to serum Cmin ratio had no correlation with clinical response. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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