A mathematical framework for the dynamic interaction of pulsatile blood, brain, and cerebrospinal fluid.

BACKGROUND: Shedding light on less-known aspects of intracranial fluid dynamics may be helpful to understand the hydrocephalus mechanism. The present study suggests a mathematical framework based on in vivo inputs to compare the dynamic interaction of pulsatile blood, brain, and cerebrospinal fluid (CSF) between the healthy subject and the hydrocephalus patient. METHOD: The input data for the mathematical formulations was pulsatile blood velocity, which was measured using cine PC-MRI. Tube law was used to transfer the created deformation by blood pulsation in the vessel circumference to the brain domain. The pulsatile deformation of brain tissue with respect to time was calculated and considered to be inlet velocity in the CSF domain. The governing equations in all three domains were continuity, Navier-Stokes, and concentration. We used Darcy law with defined permeability and diffusivity values to define the material properties in the brain. RESULTS: We validated the preciseness of the CSF velocity and pressure through the mathematical formulations with cine PC-MRI velocity, experimental ICP, and FSI simulated velocity and pressure. We used the analysis of dimensionless numbers including Reynolds, Womersley, Hartmann, and Peclet to evaluate the characteristics of the intracranial fluid flow. In the mid-systole phase of a cardiac cycle, CSF velocity had the maximum value and CSF pressure had the minimum value. The maximum and amplitude of CSF pressure, as well as CSF stroke volume, were calculated and compared between the healthy subject and the hydrocephalus patient. CONCLUSION: The present in vivo-based mathematical framework has the potential to gain insight into the less-known points in the physiological function of intracranial fluid dynamics and the hydrocephalus mechanism.

Relationship between inferior frontal sulcal hyperintensities on brain MRI, ageing and cerebral small vessel disease.

Raised signal in cerebrospinal fluid (CSF) on fluid-attenuated inversion recovery (FLAIR) may indicate raised CSF protein or debris and is seen in inferior frontal sulci on routine MRI. To explore its clinical relevance, we assessed the association of inferior frontal sulcal hyperintensities (IFSH) on FLAIR with demographics, risk factors, and small vessel disease markers in three cohorts (healthy volunteers, n=44; mild stroke patients, n=105; older community-dwelling participants from Lothian birth cohort 1936, n=101). We collected detailed clinical data, scanned all subjects on the same 3T MRI scanner and 3-dimensional FLAIR sequence and developed a scale to rate IFSH. In adjusted analyses, the IFSH score increased with age (per 10-year increase; OR 1.69; 95% CI, 1.42-2.02), and perivascular spaces score in centrum semiovale in stroke patients (OR 1.73; 95% CI, 1.13-2.69). Since glymphatic CSF clearance declines with age and drains partially via the cribriform plate to the nasal lymphatics, IFSH on 3T MRI may be a non-invasive biomarker of altered CSF clearance and justifies further research in larger, more diverse samples.

Label-Free Quantitative Proteome Profiling of Cerebrospinal Fluid from a Rat Stroke Model with Stem Cell Therapy.

Human adipose-derived mesenchymal stem cells (hAMSCs) are capable of immunomodulation and regeneration after neural injury. For these reasons, hAMSCs have been investigated as a promising stem cell candidate for stroke treatment. However, noninvasive experiments studying the effects of grafted stem cells in the host brain have not yet been reported. Cerebrospinal fluid (CSF), which can be collected without sacrificing the subject, is involved in physiological control of the brain and reflects the pathophysiology of various neurological disorders of the central nervous system (CNS). Following stem cell transplantation in a stroke model, quantitative analysis of CSF proteome changes can potentially reveal the therapeutic effect of stem cells on the host CNS. We examined hAMSC-secreted proteins obtained from serum-free culture medium by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which identified several extracellular matrix proteins, supporting the well-known active paracrine function of hAMSCs. Subsequently, we performed label-free quantitative proteomic analysis on CSF samples from rat stroke models intravenously injected with hAMSC (experimental) or phosphate buffered saline (control). In total, 524 proteins were identified; among them, 125 and 91 proteins were increased and decreased with hAMSC treatment, respectively. Furthermore, gene set enrichment analysis revealed three proteins, 14-3-3 theta, MAG, and neurocan, that showed significant increases in the hAMSC-treated model; these proteins are core members of neurotrophin signaling, nerve growth factor (NGF) signaling, and glycosaminoglycan metabolism, respectively. Subsequent histological and neurologic function experiments validated proliferative neurogenesis in the hAMSC-treated stroke model. We conclude that (i) intravenous injection of hAMSCs can induce neurologic recovery in a rat stroke model and (ii) CSF may reflect the therapeutic effect of hAMSCs. Additionally, proteins as 14-3-3 theta, MAG, and neurocan could be considered as potential CSF biomarkers of neuroregeneration. These CSF proteome profiling results would be utilized as valuable resource in further stroke studies.

Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.

INTRODUCTION: Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke. METHODS: We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants. RESULTS: After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity. CONCLUSION: Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed.

Frequency of Screening and Prevalence of Neurosyphilis in Stroke Population.

BACKGROUND AND AIMS: Syphilis and stroke are high prevalent diseases in south Brazil and estimates of concomitance and possible role of syphilis in acute stroke are lacking. Our aims are to estimate the prevalence of syphilis and neurosyphilis (NS) in a cohort of tertiary stroke center. METHODS: We reviewed all hospital records of stroke/transitory ischemic attack (TIA) using International Classification of Diseases, 10th revision, at discharge, frequency of syphilis screen, serology positivity, cerebrospinal fluid (CSF) analysis, and prevalence of NS in this stroke population applying CDC criteria. RESULTS: Between 2015 and 2016, there were 1,436 discharges for cerebrovascular events and in 78% (1,119) of these cases, some syphilis screening was performed. We have found a frequency of positive serology for syphilis of 13% (143/1,119), and higher stroke severity was the main determinant for non-screening. Applying standard NS criteria, 4.7% (53/1,119) cases with CSF analysis had NS diagnosis: 8 based on CSF-Venereal Disease Research Laboratory (VDRL) positive and 45 based on abnormal CSF white cells or protein, but CSF VDRL negative. NS VDRL positive cases were younger, had higher serum VDRL title, had more frequent HIV infection, and received NS treatment more often. Demographic and clinical characteristics were not different between NS VDRL negative and non-NS cases. CONCLUSION: Positive syphilis serology is frequent in patients with acute stroke/TIA in our region. Acute post-stroke CSF abnormalities make the diagnosis of NS difficult in the context of CSF VDRL negative.

Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke.

BACKGROUND: Emergence of the novel corona virus (severe acute respiratory syndrome (SARS)-CoV-2) in December 2019 has led to the COVID-19 pandemic. The extent of COVID-19 involvement in the central nervous system is not well established, and the presence or the absence of SARS-CoV-2 particles in the cerebrospinal fluid (CSF) is a topic of debate. CASE DESCRIPTION: We present two patients with COVID-19 and concurrent neurological symptoms. Our first patient is a 31-year-old man who had flu-like symptoms due to COVID-19 and later developed an acute-onset severe headache and loss of consciousness and was diagnosed with a Hunt and Hess grade 3 subarachnoid haemorrhage from a ruptured aneurysm. Our second patient is a 62-year-old woman who had an ischaemic stroke with massive haemorrhagic conversion requiring a decompressive hemicraniectomy. Both patients' CSF was repeatedly negative on real-time PCR analysis despite concurrent neurological disease. CONCLUSION: Our report shows that patients' CSF may be devoid of viral particles even when they test positive for COVID-19 on a nasal swab. Whether SARS-CoV-2 is present in CSF may depend on the systemic disease severity and the degree of the virus' nervous tissue tropism and should be examined in future studies.

Impact of brain volume and intracranial cerebrospinal fluid volume on the clinical outcome in endovascularly treated stroke patients.

PURPOSE: Previously, brain volume (BV) and intracranial cerebrospinal fluid volume (CSFV) have been investigated regarding clinical outcomes of subgroups of ischemic stroke patients. This study aimed to examine if the preexisting, preischemic BV and CSFV have an impact on good functional outcome and mortality in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). METHODS: Preischemic BV, CSFV, and CSFV/Total intracranial volume (TICV)-ratio were calculated with a fully automated segmentation platform. Univariate and multivariate analyses were used to study associations. RESULTS: In this retrospective study 107 subsequent AIS patients of a prospective database were included. The segmentation results of the fully automated algorithm based on non-contrast computerized tomography scans (NCCT) correlated significantly with the segmentation results obtained from 3D T1 weighted magnetic resonance images (P < 0.001). In the univariate analysis a preexisting BV (P < 0.001), preexisting CSFV (P = 0.009), and the ratio CSFV/total intracranial volume (P < 0.001) each significantly correlated with good functional outcome and mortality. However, in the multivariate regression analysis, also correcting for patient age, none of these volumes remained to correlate with these outcome parameters. CONCLUSION: In summary, an association of BV, CSFV, and the CSFV/TICV-ratio with good functional outcome and mortality in AIS treated with MT could not be established. A fully automated segmentation algorithm based on NCCT was successfully developed in-house for calculating the volumes of interest.

Central Nervous System Fungal Infection-Related Stroke: A Descriptive Study of Mold and Yeast-Associated Ischemic Stroke.

OBJECTIVE: Central nervous system (CNS) ischemic events caused by fungal infections are rare, and clinical characteristics of these ischemic events are largely unknown. The objective of this manuscript is to highlight characteristics of fungal-related strokes and describe possible mechanistic differences between CNS mold and yeast infection-related strokes. METHODS: We report a single-center retrospective case series of all adult patients who presented with concurrent CNS fungal infection and stroke between 2010 and 2018. Patients believed to have a stroke etiology due to cardioembolic, atheroembolic, or strokes nontemporally associated with a CNS fungal infection and those with incomplete stroke workups were excluded from analysis. RESULTS: Fourteen patients were identified with ischemic stroke and concurrent CNS fungal infection without other known ischemic stroke etiology. Eight patients had a CNS yeast infection, and 6 had a CNS mold infection. All patients presented with recurrent or progressive stroke symptoms. Six patients were immune-compromised. Four patients admitted to intravenous drug use. All yeast infections were identified by cerebrospinal fluid culture or immunologic studies while all but one of the mold infections required identification by tissue biopsy. Leptomeningeal enhancement was only associated with CNS yeast infections, while basal ganglia stroke was only associated with CNS mold infections. CONCLUSION: Ischemic stroke secondary to CNS fungal infections should be considered in patients with recurrent or progressive cryptogenic stroke, regardless of immune status and cerebrospinal fluid profile. CNS yeast and mold infections have slightly different stroke and laboratory characteristics and should have a distinct diagnostic method. Depending on clinical suspicion, a thorough diagnostic approach including spinal fluid analysis and biopsy should be considered.

Cerebrospinal fluid influx drives acute ischemic tissue swelling.

Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.

Combined proteomic and metabolomic analyses of cerebrospinal fluid from mice with ischemic stroke reveals the effects of a Buyang Huanwu decoction in neurodegenerative disease.

Ischemic stroke is one of the most common causes of death worldwide and is a major cause of acquired disability in adults. However, there is still a need for an effective drug for its treatment. Buyang Huanwu decoction (BHD), a traditional Chinese medicine (TCM) prescription, has long been used clinically to aid neurological recovery after stroke. To establish potential clinical indicators of BHD efficacy in stroke treatment and prognosis, we conducted a combined proteomic and metabolomic analysis of cerebrospinal fluid (CSF) samples in a mouse stroke model. CSF samples were obtained from male mice with acute ischemic stroke induced by middle cerebral ischemic/reperfusion (CI/R) injury, some of which were then treated with BHD. Label-free quantitative proteomics was conducted using nano-LC-MS/MS on an LTQ Orbitrap mass and metabolomic analysis was performed using nanoprobe NMR and UHPLC-QTOF-MS. The results showed that several proteins and metabolites were present at significantly different concentrations in the CSF samples from mice with CI/R alone and those treated with BHD. These belonged to pathways related to energy demand, inflammatory signaling, cytoskeletal regulation, Wnt signaling, and neuroprotection against neurodegenerative diseases. In conclusion, our in silico data suggest that BHD treatment is not only protective but can also ameliorate defects in pathways affected by neurological disorders. These data shed light on the mechanism whereby BHD may be effective in the treatment and prevention of stroke-related neurodegenerative disease.

Immunophenotyping of cerebrospinal fluid cells in ischaemic stroke.

BACKGROUND AND PURPOSE: Post-ischaemic immune cell invasion into the brain is well characterized in animal stroke models and contributes to neuronal damage. Therefore, it represents a promising therapeutic target. Cerebrospinal fluid (CSF) is easily accessible and may reflect cellular events within the parenchyma. However, comprehensive studies on CSF immune cells in patients with stroke are lacking. METHODS: In a retrospective cohort study, we performed extensive immune-cell profiling in CSF and peripheral blood of patients with acute ischaemic stroke and healthy controls. In patients with stroke, infarct size was quantified on follow-up imaging. RESULTS: Overall, 90 patients with ischaemic stroke and 22 controls were included in our study. After stroke, the total protein was increased (537.3 vs. 353.2 mg/L, P = 0.008) and the mean total white cell count was slightly but non-significantly elevated (1.76 vs. 0.50 cells/µL, P = 0.059). Proportions of CSF lymphocytes, monocytes and granulocytes and their respective subsets did not differ between patients with stroke and controls. In addition, there were no associations between proportions of major leukocyte subsets in CSF and the time from symptom onset to CSF sampling, infarct size or infarct localization. CONCLUSIONS: Ischaemic stroke induces only a very slight increase of CSF immune cells without changes in the composition of immune cell subsets, thus indicating that parenchymal inflammation is not sufficiently reflected in the CSF. Our findings suggest that CSF is not a major invasion route for immune cells and that CSF cell analyses are not suitable as biomarkers to guide future immune therapies for stroke.

Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke.

BACKGROUND: Neurofilament light (NFL) is a well-validated biomarker for neuronal injury and neurodegeneration. Increased cerebrospinal fluid (CSF) levels have been shown after stroke, as well as in patients with a broad range of neurodegenerative and neuroinflammatory diseases. Neurofilament heavy (NFH) belongs to the same family of structural proteins but it is less extensively studied. The potential of phosphorylated NFH (pNFH) as a stroke biomarker and for the prediction of clinical outcome is unknown. In this study, we aimed to examine the temporal pattern of NFL and pNFH concentrations in serum and CSF after acute ischemic stroke. MATERIALS AND METHODS: A quantitative Enzyme-Linked ImmunoSorbent Assay (ELISA) for pNFH was developed and tested on CSF and serum samples. NFL and pNFH were analysed in serum and CSF of acute ischemic stroke patients, who were followed over time (Day 0-1, Day 2-3, Day 7-9, three weeks, and 3-5 months after stroke). RESULTS: NFL and pNFH concentrations in serum and CSF increased after stroke, peaked during the 3rd week, and then decreased back to almost baseline levels at 3-5 months. CSF-NFL and serum-NFL correlated to the outcome measured by Barthel Index after 3-5 months, whilst no such association was seen for pNFH. DISCUSSION: These findings suggest that NFL and pNFH in both CSF and serum reflect the temporal pattern of the post ischemic axonal injury and that this process does not seem to progress after 3-5 months. CONCLUSION: NFL and pNFH in CSF and serum are promising biomarkers for axonal injury following stroke. Further studies in larger populations are needed to fully understand the progression of the neuronal damage after acute ischemic stroke and to evaluate if these biomarkers can provide additive information and how they relate to outcome.

Characterization of the rat cerebrospinal fluid proteome following acute cerebral ischemia using an aptamer-based proteomic technology.

The limited accessibility to the brain has turned the cerebrospinal fluid (CSF) into a valuable source that may contribute to the complete understanding of the stroke pathophysiology. Here we have described the CSF proteome in the hyper-acute phase of cerebral ischemia by performing an aptamer-based proteomic assay (SOMAscan) in CSF samples collected before and 30 min after male Wistar rats had undergone a 90 min Middle Cerebral Artery Occlusion (MCAO) or sham-surgery. Proteomic results indicated that cerebral ischemia acutely increased the CSF levels of 716 proteins, mostly overrepresented in leukocyte chemotaxis and neuronal death processes. Seven promising candidates were further evaluated in rat plasma and brain (CKB, CaMK2A, CaMK2B, CaMK2D, PDXP, AREG, CMPK). The 3 CaMK2 family-members and CMPK early decreased in the infarcted brain area and, together with AREG, co-localized with neurons. Conversely, CKB levels remained consistent after the insult and specifically matched with astrocytes. Further exploration of these candidates in human plasma revealed the potential of CKB and CMPK to diagnose stroke, while CaMK2B and CMPK resulted feasible biomarkers of functional stroke outcome. Our findings provided insights into the CSF proteome following cerebral ischemia and identified new outstanding proteins that might be further considered as potential biomarkers of stroke.

Comparison between cerebrospinal fluid and serum lactate concentrations in neurologic dogs with and without structural intracranial disease.

The objectives of this study were to investigate the relationship between cerebrospinal fluid lactate and serum concentrations in dogs with clinical signs of central nervous system disease and to establish if cerebrospinal fluid lactate (CSF) concentrations are higher in dogs with structural intracranial disease (Group Pos-MRI) compared to dogs that have clinical signs of intracranial disease but no structural brain disease (Group Neg-MRI) based on magnetic resonance imaging (MRI) findings. Using a prospective study canine blood and cerebrospinal fluid were collected in 24 dogs with neurological signs after undergoing brain MRI. Dogs were divided in 2 groups. No significant difference between serum lactate (1.57 ± 0.9 mmol/L) and CSF lactate concentration (1.34 ± 0.3 mmol/L) was detected. There was a direct correlation between CSF and serum lactate concentration (R = 0.731; P = 0.01). No significant difference was found in CSF lactate concentration between the 2 groups of dogs (P = 0.13).

Les objectifs de la présente étude étaient d'examiner la relation entre les concentrations de lactate du liquide céphalo-rachidien (LCR) et du sérum chez des chiens présentant des signes cliniques de pathologie du système nerveux central et établir si les concentrations de lactate du LCR sont plus élevées chez les chiens avec une maladie intracrânienne structurale (Groupe Pos-IRM) comparativement à des chiens avec des signes cliniques de maladie intracrânienne mais sans maladie structurale du cerveau (Groupe Nég-IRM) sur la base des trouvailles en imagerie par résonnance magnétique (IRM). Utilisant une étude prospective, du sang canin et du LCR ont été prélevés chez 24 chiens avec des signes neurologiques après un examen par IRM du cerveau. Les chiens ont été séparés en deux groupes. Aucune différence significative ne fut détectée entre les concentrations de lactate sérique (1,57 ± 0,9 mmol/L) et de lactate du LCR (1,34 ± 0,3 mmol/L). Il y avait une corrélation directe entre les concentrations de lactate du LCR et du sérum (R = 0,731; P = 0,01). Aucune différence significative dans la concentration de lactate du LCR ne fut trouvée entre les deux groupes de chiens (P = 0,13).(Traduit par Docteur Serge Messier).

Role of PARK7 and NDKA in stroke management: a review of PARK7 and NDKA as stroke biomarkers.

AIM: Biomarkers are molecules measured in plasma, serum or other body fluids to characterize a disease. PARK7 and NDKA roles in the management of stroke are still on study. Therefore, their potentials need to be developed in totality. The aim of this review is to demonstrate that PARK7 and NDKA could present more clinical important information as biomarkers for management of stroke disease. Main contents: Four main aspects of PARK7 and NDKA are exploited in this review. First, their diagnostic value is discussed in order to demonstrate their possible role as stroke diagnosis markers. Second, this article will exploit the correlation of both markers with time, by showing their dynamic changes in serum and plasma. Third, it describes the observed relationship of their levels with NIH Stroke Scale. The last aspect visits the possibility of their implementation in stroke therapy. CONCLUSION: This article explores recent findings and proposes the potential roles that PARK7 and NDKA play in the management of acute stroke disease.

Procarboxypeptidase U (proCPU, TAFI, proCPB2) in cerebrospinal fluid during ischemic stroke is associated with stroke progression, outcome and blood-brain barrier dysfunction.

Essentials Little is known of procarboxypeptidase U (proCPU) in cerebrospinal fluid (CSF) of stroke patients. ProCPU levels were studied in CSF of controls and non-thrombolyzed acute ischemic stroke patients. ProCPU is elevated in CSF of stroke patients compared with controls. ProCPU in CSF correlates with stroke progression, outcome, and blood-brain barrier dysfunction. SUMMARY: Background Procarboxypeptidase U (proCPU, TAFI, proCPB2), the zymogen of CPU, which is a potent antifibrinolytic enzyme and a modulator of inflammation, has previously been investigated in plasma of stroke patients, but so far, no information on the proCPU levels in cerebrospinal fluid (CSF) during acute ischemic stroke (AIS) is available. Objectives This case-control observational study investigates proCPU in CSF of AIS patients compared with controls with an intact blood-brain barrier (BBB) and evaluates the relationship of CSF/plasma proCPU ratios with stroke parameters. Methods A sensitive HPLC-based enzymatic assay was used to determine proCPU levels in CSF of non-thrombolyzed patients in the hyperacute phase (< 24 h after onset) of AIS (n = 72). Individuals (n = 32) without stroke, an intact BBB and no apparent abnormalities in biochemical and microbiological tests, served as controls. Relations between the CSF/plasma proCPU ratio and (i) stroke severity, (ii) stroke progression/recurrence, (iii) stroke outcome and (iv) BBB dysfunction (CSF/serum albumin ratio) were assessed. Results Mean (SEM) proCPU levels were elevated in the CSF of stroke patients compared with controls (4.36 (0.23) U L-1 vs. 3.50 (0.23) U L-1 ). Higher median [IQR] CSF/plasma proCPU ratios were found in patients with stroke progression ((6.0 [4.2-6.9]) × 10-3 ) and poor outcome ((6.4 [3.9-7.0]) × 10-3 ) after 3 months (modified Rankin Scale; mRS > 3) compared with patients without progression ((3.9 [2.7-5.4]) × 10-3 ) or better outcome ((4.0 [2.8-5.0]) × 10-3 ). In stroke patients with a disrupted BBB, proCPU ratios were higher compared with stroke patients with an intact BBB ((6.4 [5.8-9.0]) × 10-3 vs. (3.7 [2.8-5.0]) × 10-3 ). Conclusions ProCPU is increased in CSF during hyperacute ischemic stroke and is associated with stroke progression and outcome after 3 months, most likely due to BBB dysfunction in the hyperacute phase of ischemic stroke.

Vascular diseases and bleedings.

Diseases of the central nervous system that are caused by an underlying vascular pathology typically result in either hemorrhage or ischemia. Most prominent entities include spontaneous subarachnoid hemorrhage, spontaneous intracerebral hemorrhage, and ischemic stroke. For anatomic reasons, cerebrospinal fluid (CSF) qualifies as body fluid for the exploration of biomarkers in these disorders. Even though in subarachnoid hemorrhage a few CSF parameters have been established for routine diagnostic purposes, there is still an unmet need and broad interest in the identification of molecules that would allow further insight into disease mechanisms and supplement patients' medical care. This chapter provides an overview on what is presently known about CSF biomarkers in spontaneous subarachnoid hemorrhage, spontaneous intracerebral hemorrhage, and ischemic stroke. We recapitulate current evidence on established diagnostic tests, discuss the role of various CSF molecules in the pathophysiology of these diseases, and illuminate their potential use in future clinical practice. Furthermore, we address methodologic aspects as well as shortcomings of research in this field.

Neurogranin and tau in cerebrospinal fluid and plasma of patients with acute ischemic stroke.

BACKGROUND: While neurogranin has no value as plasma biomarker for Alzheimer's disease, it may be a potential blood biomarker for traumatic brain injury. This evokes the question whether there are changes in neurogranin levels in blood in other conditions of brain injury, such as acute ischemic stroke (AIS). METHODS: We therefore explored neurogranin in paired cerebrospinal fluid (CSF)/plasma samples of AIS patients (n = 50) from a well-described prospective study. In parallel, we investigated another neuronal protein, i.e. tau, which has already been suggested as potential AIS biomarker in CSF and blood. ELISA as well as Single Molecule Array (Simoa) technology were used for the biochemical analyses. Statistical analyses included Shapiro-Wilk testing, Mann-Whitney analyses and Pearson's correlation analysis. RESULTS: In contrast to tau, of which high levels in both CSF and plasma were related to stroke characteristics like severity and long-term outcome, plasma neurogranin levels were only correlated with infarct volume. Likewise, CSF neurogranin levels were significantly higher in patients with an infarct volume > 5 mL than in patients with smaller infarct volumes. Finally, neurogranin and tau were significantly correlated in CSF, whereas a weaker relationship was observed in plasma. CONCLUSIONS: These findings indicate that although plasma and CSF neurogranin may reflect the volume of acute cerebral ischemia, this synaptic protein is less likely to be a potential AIS biomarker. Levels of tau correlated with severity and outcome of stroke in both plasma and CSF, in the present study as well as previous reports, confirming the potential of tau as an AIS biomarker.