Visinin-like protein-1 level is associated with short-term functional outcome of acute ischemic stroke: A prospective cohort study.

Stroke is a serious disease that can lead to disability and death in adults, and the prediction of functional outcome is important in the management of acute ischemic stroke (AIS). Blood biomarker is a promising technique, for the measurement is fast, cheap and convenient. Visinin-like protein-1 (VILIP-1) is a classic stroke biomarker, thus we tried to investigate the predictive value of VILIP-1 for early functional outcomes of AIS.A total of 70 AIS patients were enrolled in our study. Venous blood samples of all patients were taken at day 3 after admission to the stroke unit, and levels of serum VILIP-1 were analyzed by the use of the enzyme-linked immunosorbent assay. All subjects underwent diffusion weighted imaging (DWI) of the brain MRI scanning at 72 hours after stroke onset, and infarct volumes were calculated. Initial neurological status was evaluated by the National Institutes of Health Stroke Scale (NIHSS) on admission. The short-term functional outcome was graded by the modified Rankin Scale (mRS) at discharge from the hospital. Baseline data between the favorable outcome group and poor outcome group were compared, and univariate and multivariable logistic regression analysis were used to identify risk factors of early functional outcome of AIS.The multivariate logistic regression analysis showed age, initial NIHSS scores and levels of VILIP had a strong association with poor clinical outcomes.Levels of serum VILIP-1 are associated with short-term functional outcomes in patients with AIS.

Clinical usefulness of brain-derived neurotrophic factor and visinin-like protein-1 in early diagnostic tests for acute stroke.

OBJECTIVES: Lack of a rapid biochemical test for acute stroke is a limitation in the diagnosis and management of acute stroke. The aim of this study is to evaluate the efficacy of BDNF and VILIP-1 as diagnostic markers in acute ischemic stroke and as predictors of mortality. METHODS: The study included 75 patients with acute ischemic stroke older than 18 years. During the same period, 28 normal controls were recruited from the hospital ED. Blood samples were collected from all patients at admission to determine the levels of VILIP-1 and BDNF. RESULTS: The mean VILIP-1 levels in the study and control groups were 0.547 ±â€¯0.081 and 0.515 ±â€¯0.035 ng/mL, respectively, and the difference was not significant (p = 0.071). The mean BDNF levels in the study and control groups were 3.89 ±â€¯2.05 ng/mL and 14.9 ±â€¯4.7 ng/mL, respectively, and the level was significantly (p < 0.0001) lower in the stroke patients. CONCLUSION: The BDNF level showed a significant ability to discriminate stroke and control patients but did not predict mortality. The VILIP-1 level showed insignificant ability to discriminate stroke patients and again did not predict mortality.

A novel method for the rapid detection of post-translationally modified visinin-like protein 1 in rat models of brain injury.

BACKGROUND: Although elevated serum levels of visinin-like protein 1 (VILIP-1), a neuron-specific calcium sensor protein, are associated with ischaemic stroke, only a single study has evaluated VILIP-1 as a biomarker of traumatic brain injury (TBI). The current proof-of-concept study was designed to determine whether serum VILIP-1 levels increase post-injury in a well-characterized rat unilateral cortical contusion model. METHODS: Lateral flow devices (LFDs) rapidly (< 20 min) detected trace serum levels (pg/mL) of VILIP-1 in a small input sample volume (10 µL). Temporal profiles of serum levels at baseline and post-injury were measured in male Sprague Dawley rats subjected to very mild-, mild unilateral-cortical contusion, or naïve surgery and in male Sprague Dawley rats following a diffuse TBI or sham surgery. RESULTS: Mean serum levels were significantly elevated by 0.5 h post-injury and remained so throughout the temporal profile compared with baseline in very mild and mild unilateral contusions but not in naïve surgeries. Serum levels were also elevated in a small cohort of animals subjected to a diffuse TBI injury. CONCLUSIONS: Overall, the current study demonstrates that the novel LFD is a reliable and rapid point-of-care diagnostic for the detection and quantification of serum levels of UB-VILIP-1 in a clinically relevant time frame.

Serum visinin-like protein-1 in concussed professional ice hockey players.

PRIMARY OBJECTIVE: Visinin-like protein-1 (VILIP-1) has shown potential utility as a biomarker for neuronal injury in cerebrospinal fluid. This study investigated serum VILIP-1 as a diagnostic and prognostic marker in sports-related concussion. METHODS: This multi-centre prospective cohort study involved the 12 teams of the professional ice hockey league in Sweden. A total of 288 players consented to participate in the study. Thirty-five players sustained concussions, of whom 28 underwent repeated blood samplings at 1, 12, 36 and 144 hours after the trauma or when the player returned to play (7-90+ days). MAIN OUTCOMES AND RESULTS: The highest levels of VILIP-1 were measured 1 hour after concussion and the levels decreased during rehabilitation, reaching a minimum level at the 36-hour sampling. However, the levels of serum VILIP-1 at 1 hour after concussion were not significantly higher than pre-season baseline values. Serum levels of VILIP-1 1 hour post-concussion did not correlate with the number of days for the concussion symptoms to resolve. Further, serum levels of VILIP-1 increased after a friendly game in players who were not concussed. CONCLUSIONS: These results provide evidence that serum VILIP-1 may not be a useful biomarker for diagnosis and prognosis of sports-related concussion.

Serum and cerebrospinal fluid levels of visinin-like protein-1 in acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has recently been recognized as an encephalopathy subtype. Typical clinical symptoms of AESD are biphasic seizures, and MRI findings show reduced subcortical diffusion during clustering seizures with unconsciousness after the acute phase. Visinin-like protein-1 (VILIP-1) is a recently discovered protein that is abundant in the central nervous system, and some reports have shown that VILIP-1 may be a prognostic biomarker of conditions such as Alzheimer's disease, stroke, and brain injury. METHODS: However, there have been no reports regarding serum and cerebrospinal fluid (CSF) levels of VILIP-1 in patients with AESD. We measured the serum and CSF levels of VILIP-1 in patients with AESD, and compared the levels to those in patients with prolonged febrile seizures (FS). RESULTS: Both serum and CSF levels of VILIP-1 were significantly higher in patients with AESD than in patients with prolonged FS. Serum and CSF VILIP-1 levels were normal on day 1 of AESD. CONCLUSIONS: Our results suggest that both serum and CSF levels of VILIP-1 may be one of predictive markers of AESD.

Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease.

OBJECTIVE: There is a growing need to identify cerebrospinal fluid (CSF) markers that can detect Alzheimer's disease (AD) pathology in cognitively normal individuals because it is in this population that disease-modifying therapies may have the greatest chance of success. While AD pathology is estimated to begin ~10-15 years prior to the onset of cognitive decline, substantial neuronal loss is present by the time the earliest signs of cognitive impairment appear. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. Here we investigate CSF VILIP-1 and VILIP-1/amyloid-ß42 (Aß42) ratio as diagnostic and prognostic markers in early AD. METHODS: We assessed CSF levels of VILIP-1, tau, phosphorylated-tau181 (p-tau181), and Aß42 in cognitively normal controls (CNC) (n = 211), individuals with early symptomatic AD (n = 98), and individuals with other dementias (n = 19). Structural magnetic resonance imaging (n = 192) and amyloid imaging with Pittsburgh Compound-B (n = 156) were obtained in subsets of this cohort. Among the CNC cohort, 164 individuals had follow-up annual cognitive assessments for 2-3 years. RESULTS: CSF VILIP-1 levels differentiated individuals with AD from CNC and individuals with other dementias. CSF VILIP-1 levels correlated with CSF tau, p-tau181, and brain volumes in AD. VILIP-1 and VILIP-1/Aß42 predicted future cognitive impairment in CNC over the follow-up period. Importantly, CSF VILIP-1/Aß42 predicted future cognitive impairment at least as well as tau/Aß42 and p-tau181/Aß42. INTERPRETATION: These findings suggest that CSF VILIP-1 and VILIP-1/Aß42 offer diagnostic utility for early AD, and can predict future cognitive impairment in cognitively normal individuals similarly to tau and tau/Aß42, respectively.

Determination of serum visinin like protein-1 and its potential for the diagnosis of brain injury due to the stroke: a pilot study.

BACKGROUND: The current diagnosis of stroke relies on clinical examination by a physician supplemented by various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in acute settings to diagnosis stroke, differentiate between stroke types, and ideally predict an initial/recurring stroke would be extremely valuable. The diagnosis of stroke is currently hampered by delay due to lack of a suitable tool for rapid, accurate and analytically sensitive biomarker - based testing. There is a clear need for further assay development and clinical validation in this area (acute stroke setting) in order to improve patient outcomes and quality of life. Visinin like protein 1 (VILIP-1) is a newly discovered CNS-abundant protein which has shown promise in experimental studies, for early stroke diagnosis. However, to date there is no clinical study that has measured VILIP-1 in sera as a marker of stroke. AIM: To develop an assay for the determination of VILIP-1 in human serum, and to investigate its clinical relevance as a marker of ischemic stroke. DESIGN AND METHODS: A new sandwich ELISA was developed, introduced and clinically tested. Mean spiking recovery was 98%. The mean recovery for dilution linearity was 93%. The limit of detection of the assay was 0.01 mcg/l; the intraassay and interassay coefficient of variation (CV) were always less than 10%. The study was approved by the Ethics Commission of the Hospital Sternberk, Czech Republic. A total of 17 healthy individuals (9 men and 8 women, age 64.0 ± 13.0) and 16 individuals with ischemic stroke (10 men and 6 women, age 63.0±11.5) were recruited for our study. The criteria of stroke were proposed by the National Czech Standard. All individuals had blood samples drawn, and VILIP-1 analysis and CT and/or MRI were performed. Results. VILIP-1 serum level significantly differentiated healthy subjects from patients with stroke (P<0.01). All individuals with stroke had VILIP-1 serum values higher than > 0.05 mcg/l, healthy had values below this value. The diagnostic efficacy of serum VILIP-1 was very significant (sensitivity 100%, specificity 100% at 0.093 mcg/l VILIP-1 serum values, AUC 1.0 (CI 0.93-1.0, P<0.01), Chi-squared in the frequency table was 33 (P<0.01). CONCLUSION: We have introduced a new analytical tool for the study of VILIP-1. Our results support the hypothesis that serum VILIP-1 may be associated with ischemic stroke. The ELISA VILIP-1 assay offers a new research tool for the diagnosis and pathophysiology of stroke and other CNS diseases.

Identification of novel brain biomarkers.

BACKGROUND: The diagnosis of diseases leading to brain injury, such as stroke, Alzheimer disease, and Parkinson disease, can often be problematic. In this study, we pursued the discovery of biomarkers that might be specific and sensitive to brain injury. METHODS: We performed gene array analyses on a mouse model to look for biomarkers that are both preferentially and abundantly produced in the brain. Via bioinformatics databases, we identified the human homologs of genes that appeared abundant in brain but not in other tissues. We then confirmed protein production of the genes via Western blot of various tissue homogenates and assayed for one of the markers, visinin-like protein 1 (VLP-1), in plasma from patients after ischemic stroke. RESULTS: Twenty-nine genes that were preferentially and abundantly expressed in the mouse brain were identified; of these 29 genes, 26 had human homologs. We focused on 17 of these genes and their protein products on the basis of their molecular characteristics, novelty, and/or availability of antibodies. Western blot showed strong signals in brain homogenates for 13 of these proteins. Tissue specificity was tested by Western blot on a human tissue array, and a sensitive and quantitative sandwich immunoassay was developed for the most abundant gene product observed in our search, VLP-1. VLP-1 was detected in plasma of patients after stroke and in cerebrospinal fluid of a rat model of stroke. CONCLUSIONS: The use of relative mRNA production appears to be a valid method of identifying possible biomarkers of tissue injury. The tissue specificity suggested by gene expression was confirmed by Western blot. One of the biomarkers identified, VLP-1, was increased in a rat model of stroke and in plasma of patients after stroke. More extensive, prospective studies of the candidate biomarkers identified appear warranted.