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Biomedicines
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Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers
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Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 23181

Special Issue Editors

Prof. Dr. Joanna Matowicka-Karna

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Guest Editor
Department of Clinical Laboratory Diagnostics, Medical University of Białystok, 15A Jerzego Waszyngtona St., 15-269 Białystok, Poland
Interests: cerebrospinal fluid; inflammation markers; cytokines
Dr. Olga M. Koper-Lenkiewicz

E-Mail Website
Guest Editor
Department of Clinical Laboratory Diagnostics, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, 15-089 Białystok, Poland
Interests: cerebrospinal fluid; biomarker; central nervous system diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Joanna Kamińska

E-Mail Website
Guest Editor
Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland
Interests: cancer; central nervous system diseases; cerebrospinal fluid; cytokines; biomarker; inflammation markers
Special Issues, Collections and Topics in MDPI journals
Dr. Ewa Kowalewska

E-Mail Website
Guest Editor
Department of Clinical Laboratory Diagnostics, Medical University of Białystok, 15A Jerzego Waszyngtona St., 15-269 Białystok, Poland
Interests: cerebrospinal fluid; biomarker; central nervous system diseases; brain tumors

Special Issue Information

Dear Colleagues,

Cerebrospinal fluid (CSF) surrounds the brain and the spinal cord. It is a colorless, transparent liquid filling the ventricles of the brain, subarachnoid space, as well as the canal of the spinal cord. It plays an important role in preserving CNS homeostasis. Sustaining this homeostasis is ensured by the presence of two barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). To some extent, these two barriers isolate the CNS from the blood environment, which is characterized by relatively large dynamics of change. BCSFB is functionally limited to the choroid plexus and involves a non-linear interaction between the diffusion of blood proteins into the CSF and its flow rate. The BBB is a physical barrier with a tight location between blood and nervous tissue.

Due to the fact that CSF is the closest fluid to the brain, it directly reflects alterations within the CNS and, thus, provides a valuable opportunity to detect CNS diseases of various etiologies. The molecular analysis of CSF could also be useful in evaluating the progress of and prognosis for particular CNS diseases. Finally, by indicating and measuring drug-related biomarkers, the most effective therapeutic strategy could be designated. Therefore, we call for original papers, reviews, and other forms of scientific communication to provide new findings regarding the CSF-related molecular biomarkers, which could be useful in early diagnosis, disease prevention, drug target identification, drug response, etc., in both primary and secondary diseases that affect CNS. Potential topics include, but are not limited to, central nervous system diseases caused by trauma, infections, COVID-19, degeneration, structural defects, CNS tumors, hematological malignancies, autoimmune diseases, trigeminal neuralgia, cerebrovascular disorder, and stroke. Molecular biomarkers related to the blood-brain barrier and the blood-cerebrospinal fluid barrier are also welcomed.

Prof. Dr. Joanna Matowicka-Karna
Dr. Olga M. Koper-Lenkiewicz
Dr. Joanna Kamińska
Dr. Ewa Kowalewska
Guest Editors

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Keywords

  • blood-brain barrier
  • blood-cerebrospinal fluid barrier
  • central nervous system disease
  • cerebrospinal fluid (CSF)
  • CSF disease-related biomarker
  • CSF drug-related biomarker
  • CSF molecular biomarker
  • pharmacotherapy

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Published Papers (6 papers)

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Research

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20 pages, 1433 KiB  
Article
Cerebrospinal Fluid and Serum Biomarker Insights in Aneurysmal Subarachnoid Haemorrhage: Navigating the Brain–Heart Interrelationship for Improved Patient Outcomes
by Małgorzata Burzyńska, Agnieszka Uryga, Rafał Załuski, Anna Goździk, Barbara Adamik, Chiara Robba and Waldemar Goździk
Biomedicines 2023, 11(10), 2835; https://doi.org/10.3390/biomedicines11102835 - 19 Oct 2023
Cited by 2 | Viewed by 1153
Abstract
The pathophysiological mechanisms underlying severe cardiac dysfunction after aneurysmal subarachnoid haemorrhage (aSAH) remain poorly understood. In the present study, we focused on two categories of contributing factors describing the brain–heart relationship. The first group includes brain-specific cerebrospinal fluid (CSF) and serum biomarkers, as [...] Read more.
The pathophysiological mechanisms underlying severe cardiac dysfunction after aneurysmal subarachnoid haemorrhage (aSAH) remain poorly understood. In the present study, we focused on two categories of contributing factors describing the brain–heart relationship. The first group includes brain-specific cerebrospinal fluid (CSF) and serum biomarkers, as well as cardiac-specific biomarkers. The secondary category encompasses parameters associated with cerebral autoregulation and the autonomic nervous system. A group of 15 aSAH patients were included in the analysis. Severe cardiac complications were diagnosed in seven (47%) of patients. In the whole population, a significant correlation was observed between CSF S100 calcium-binding protein B (S100B) and brain natriuretic peptide (BNP) (rS = 0.62; p = 0.040). Additionally, we identified a significant correlation between CSF neuron-specific enolase (NSE) with cardiac troponin I (rS = 0.57; p = 0.025) and BNP (rS = 0.66; p = 0.029), as well as between CSF tau protein and BNP (rS = 0.78; p = 0.039). Patients experiencing severe cardiac complications exhibited notably higher levels of serum tau protein at day 1 (0.21 ± 0.23 [ng/mL]) compared to those without severe cardiac complications (0.03 ± 0.04 [ng/mL]); p = 0.009. Impaired cerebral autoregulation was noted in patients both with and without severe cardiac complications. Elevated serum NSE at day 1 was related to impaired cerebral autoregulation (rS = 0.90; p = 0.037). On the first day, a substantial, reciprocal correlation between heart rate variability low-to-high frequency ratio (HRV LF/HF) and both GFAP (rS = −0.83; p = 0.004) and S100B (rS = −0.83; p = 0.004) was observed. Cardiac and brain-specific biomarkers hold the potential to assist clinicians in providing timely insights into cardiac complications, and therefore they contribute to the prognosis of outcomes. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers)
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12 pages, 1476 KiB  
Article
Adiponectin Alleviates Cell Injury due to Cerebrospinal Fluid from Multiple Sclerosis Patients by Inhibiting Oxidative Stress and Proinflammatory Response
by Marta Mallardo, Elisabetta Signoriello, Giacomo Lus, Aurora Daniele and Ersilia Nigro
Biomedicines 2023, 11(6), 1692; https://doi.org/10.3390/biomedicines11061692 - 12 Jun 2023
Cited by 2 | Viewed by 1237
Abstract
Multiple sclerosis (MS) is the most common disabling neurological disease characterized by chronic inflammation and neuronal cell viability impairment. Based on previous studies reporting that adiponectin exhibits neuroprotective effects in some models of neurodegenerative diseases, we analyzed the effects of AdipoRon treatment, alone [...] Read more.
Multiple sclerosis (MS) is the most common disabling neurological disease characterized by chronic inflammation and neuronal cell viability impairment. Based on previous studies reporting that adiponectin exhibits neuroprotective effects in some models of neurodegenerative diseases, we analyzed the effects of AdipoRon treatment, alone or in combination with the cerebrospinal fluid of patients with MS (MS-CSF), to verify whether this adipokine acts on the basal neuronal cellular processes. To this aim, SH-SY5Y and U-87 cells (models of neuronal and glial cells, respectively) were exposed to MS-CSF alone or in co-treatment with AdipoRon. The cell viability was determined via MTT assay, and the possible underlying mechanisms were investigated via the alterations of oxidative stress and inflammation. MTT assay confirmed that AdipoRon alone did not affect the viability of both cell lines; whereas, when used in combination with MS-CSF, it reduces MS-CSF inhibitory effects on the viability of both SH-SY5Y and U-87 cell lines. In addition, MS-CSF treatment causes an increase in pro-inflammatory cytokines, whereas it determines the reduction in anti-inflammatory IL-10. Interestingly, the co-administration of AdipoRon counteracts the MS-CSF-induced production of pro-inflammatory cytokines, whereas it determines an enhancement of IL-10. In conclusion, our data suggest that AdipoRon counteracts the cytotoxic effects induced by MS-CSF on SH-SY5Y and U-87 cell lines and that one of the potential molecular underlying mechanisms might occur via reduction in oxidative stress and inflammation. Further in vivo and in vitro studies are essential to confirm whether adiponectin could be a neuro-protectant candidate against neuronal cell injury. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers)
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14 pages, 2394 KiB  
Article
Inflammatory Markers as Predictors of Shunt Dependency and Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage
by Nina Rostgaard, Markus Harboe Olsen, Tenna Capion, Nanna MacAulay and Marianne Juhler
Biomedicines 2023, 11(4), 997; https://doi.org/10.3390/biomedicines11040997 - 23 Mar 2023
Cited by 8 | Viewed by 1978
Abstract
The mechanisms underlying post-hemorrhagic hydrocephalus (PHH) development following subarachnoid hemorrhage (SAH) are not fully understood, which complicates informed clinical decisions regarding the duration of external ventricular drain (EVD) treatment and prevents the prediction of shunt-dependency in the individual patient. The aim of this [...] Read more.
The mechanisms underlying post-hemorrhagic hydrocephalus (PHH) development following subarachnoid hemorrhage (SAH) are not fully understood, which complicates informed clinical decisions regarding the duration of external ventricular drain (EVD) treatment and prevents the prediction of shunt-dependency in the individual patient. The aim of this study was to identify potential inflammatory cerebrospinal fluid (CSF) biomarkers of PHH and, thus, shunt-dependency and functional outcome in patients with SAH. This study was a prospective observational study designed to evaluate inflammatory markers in ventricular CSF. In total, 31 Patients with SAH who required an EVD between June 2019 and September 2021 at the Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark, were included. CSF samples were collected twice from each patient and analyzed for 92 inflammatory markers via proximity extension assay (PEA), and the prognostic ability of the markers was investigated. In total, 12 patients developed PHH, while 19 were weaned from their EVD. Their 6-month functional outcome was determined with the modified Rankin Scale. Of the 92 analyzed inflammatory biomarkers, 79 were identified in the samples. Seven markers (SCF, OPG, LAP TGFβ1, Flt3L, FGF19, CST5, and CSF1) were found to be predictors of shunt dependency, and four markers (TNFα, CXCL5, CCL20, and IL8) were found to be predictors of functional outcome. In this study, we identified promising inflammatory biomarkers that are able to predict (i) the functional outcome in patients with SAH and (ii) the development of PHH and, thus, the shunt dependency of the individual patients. These inflammatory markers may have the potential to be employed as predictive biomarkers of shunt dependency and functional outcome following SAH and could, as such, be applied in the clinic. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers)
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12 pages, 1255 KiB  
Article
Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement
by Mariola Świderek-Matysiak, Magdalena Oset, Małgorzata Domowicz, Grażyna Galazka, Magdalena Namiecińska and Mariusz Stasiołek
Biomedicines 2023, 11(2), 425; https://doi.org/10.3390/biomedicines11020425 - 1 Feb 2023
Cited by 5 | Viewed by 2337
Abstract
Background: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS). Methods: In total, 242 [...] Read more.
Background: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS). Methods: In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI. The non-MS patients were subdivided into systemic inflammatory diseases with CNS involvement (SID) or cerebrovascular diseases (CVD) or other non-inflammatory diseases (NID). All samples were analyzed for the presence of oligoclonal bands and ELISA was performed for detection of: INF gamma, IL-6, neurofilaments light chain (NF-L), GFAP, CHI3L1, CXCL13, and osteopontin. Results: The level of IL-6 (p = 0.024), osteopontin (p = 0.0002), and NF-L (p = 0.002) was significantly different among groups. IL-6 (p = 0.0350) and NF-L (p = 0.0015) level was significantly higher in SID compared to NID patients. A significantly higher level of osteopontin (p = 0.00026) and NF-L (p = 0.002) in MS compared to NID population was noted. ROC analysis found weak diagnostic power for osteopontin and NFL-L. Conclusions: The classical and non-standard markers of inflammatory process and neurodegeneration do not allow for sufficient differentiation between MS and non-MS inflammatory CNS disorders. Weak diagnostic power observed for the osteopontin and NF-L needs to be further investigated. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers)
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Review

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23 pages, 4818 KiB  
Review
Cerebrospinal Fluid–Basic Concepts Review
by Natalia Czarniak, Joanna Kamińska, Joanna Matowicka-Karna and Olga Martyna Koper-Lenkiewicz
Biomedicines 2023, 11(5), 1461; https://doi.org/10.3390/biomedicines11051461 - 17 May 2023
Cited by 16 | Viewed by 9944
Abstract
Cerebrospinal fluid plays a crucial role in protecting the central nervous system (CNS) by providing mechanical support, acting as a shock absorber, and transporting nutrients and waste products. It is produced in the ventricles of the brain and circulates through the brain and [...] Read more.
Cerebrospinal fluid plays a crucial role in protecting the central nervous system (CNS) by providing mechanical support, acting as a shock absorber, and transporting nutrients and waste products. It is produced in the ventricles of the brain and circulates through the brain and spinal cord in a continuous flow. In the current review, we presented basic concepts related to cerebrospinal fluid history, cerebrospinal fluid production, circulation, and its main components, the role of the blood–brain barrier and the blood–cerebrospinal fluid barrier in the maintenance of cerebrospinal fluid homeostasis, and the utility of Albumin Quotient (QAlb) evaluation in the diagnosis of CNS diseases. We also discussed the collection of cerebrospinal fluid (type, number of tubes, and volume), time of transport to the laboratory, and storage conditions. Finally, we briefly presented the role of cerebrospinal fluid examination in CNS disease diagnosis of various etiologies and highlighted that research on identifying cerebrospinal fluid biomarkers indicating disease presence or severity, evaluating treatment effectiveness, and enabling understanding of pathogenesis and disease mechanisms is of great importance. Thus, in our opinion, research on cerebrospinal fluid is still necessary for both the improvement of CNS disease management and the discovery of new treatment options. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers)
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Other

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13 pages, 2005 KiB  
Technical Note
A Minimally-Invasive Method for Serial Cerebrospinal Fluid Collection and Injection in Rodents with High Survival Rates
by Jingrong Regina Han, Yu Yang, Tianshu William Wu, Tao-Tao Shi, Wenlu Li and Yilong Zou
Biomedicines 2023, 11(6), 1609; https://doi.org/10.3390/biomedicines11061609 - 1 Jun 2023
Cited by 3 | Viewed by 4498
Abstract
Cerebrospinal fluid (CSF) is an important sample source for diagnosing diseases in the central nervous system (CNS), but collecting and injecting CSF in small animals is technically challenging and often results in high mortality rates. Here, we present a cost-effective and efficient method [...] Read more.
Cerebrospinal fluid (CSF) is an important sample source for diagnosing diseases in the central nervous system (CNS), but collecting and injecting CSF in small animals is technically challenging and often results in high mortality rates. Here, we present a cost-effective and efficient method for accessing the CSF in live rodents for fluid collection and infusion purposes. The key element of this protocol is a metal needle tool bent at a unique angle and length, allowing the successful access of the CSF through the foramen magnum. With this method, we can collect 5–10 µL of the CSF from mice and 70–100 µL from rats for downstream analyses, including mass spectrometry. Moreover, our minimally-invasive procedure enables iterative CSF collection from the same animal every few days, representing a significant improvement over prior protocols. Additionally, our method can be used to inject solutions into mice cisterna magna with high success rates and high postoperative recovery rates. In summary, we provide an efficient and minimally-invasive protocol for collecting and infusing reagents into the CSF in live rodents. We envision this protocol will facilitate biomarker discovery and drug development for diseases in the central nervous system. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid: The Potential for Molecular Disease-Related and Drug-Related Biomarkers)
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