Tenascin-C in patients with central nervous system infections.

BACKGROUND: The extracellular matrix protein tenascin-C has been discovered to be an important regulator of the response to tissue injury and repair in cerebrovascular diseases. This study investigated if tenascin-C is released in response to infections in the central nervous system (CNS). METHODS: Tenascin-C concentration in the cerebrospinal fluid (CSF) was measured in patients, (>18 years) with and without CNS infections, admitted to a department of infectious diseases in Denmark. CSF tenascin-C was measured on the Meso-scale platform. RESULTS: 174 patients were included of which 140 were diagnosed with a CNS infection and 34 where this was ruled out (control group). Median CSF tenascin-C levels were significantly higher among patients with bacterial meningitis (147 pg/mL), viral meningitis (33 mg/mL), viral encephalitis (39 pg/mL) and Lyme neuroborreliosis (45 pg/mL) when compared to controls (21 pg/mL). Correlations between tenascin-C and CSF markers of inflammation and age were only moderate. CONCLUSION: Levels of CSF tenascin-C are higher among patients with bacterial and viral neuroinfections, already on admission, but exhibit only a modest correlation with baseline indices of neuroinflammation. CSF tenascin-C is highest among patients with bacterial meningitis compared to the other CNS infections. Patients with unfavorable outcomes presented with higher median CSF tenascin-C than their counterparts.

Cerebrospinal Fluid Concentrations of Extracellular Matrix Proteins in Alzheimer's Disease.

BACKGROUND: Brevican, neurocan, tenascin-C, and tenascin-R are extracellular matrix (ECM) proteins that are mainly expressed in the brain. They play important roles in proliferation and migration of neurons and other cell types in the brain. These ECM proteins may also be involved in various pathologies, including reactive gliosis. OBJECTIVE: The aim of the study was to investigate if ECM protein concentrations in cerebrospinal fluid (CSF) are linked to the neurodegenerative process in Alzheimer's disease (AD). METHODS: Lumbar CSF samples from a non-AD control group (n = 50) and a clinically diagnosed AD group (n = 42), matched for age and gender, were analyzed using commercially available ELISAs detecting ECM proteins. Mann-Whitney U test was used to examine group differences, while Spearman's rho test was used for correlations. RESULTS: Brevican, neurocan, tenascin-R, and tenascin-C concentrations in AD patients did not differ compared to healthy controls or when the groups were dichotomized based on the Aß42/40 cut-off. CSF tenascin-C and tenascin-R concentrations were significantly higher in women than in men in the AD group (p = 0.02). CONCLUSION: ECM proteins do not reflect AD-pathology in CSF. CSF tenascin-C and tenascin-R upregulation in women possibly reveal sexual dimorphism in the central nervous system immunity during AD.

Dynamics of extracellular matrix proteins in cerebrospinal fluid and serum and their relation to clinical outcome in human traumatic brain injury.

Background Brevican, neurocan, tenascin-C and tenascin-R are extracellular matrix proteins present in brain that show increased expression in experimental animal models of brain injury. However, little is known about the dynamics of these proteins in human body fluids, such as cerebrospinal fluid (CSF) and serum, after traumatic brain injury (TBI). The aims of this study were to investigate if matrix proteins in CSF and serum are associated with functional outcome following traumatic brain injury, if their concentrations change over time and to compare their levels between brain injured patients to controls. Methods In total, 42 traumatic brain injury patients, nine healthy controls and a contrast group consisting of 38 idiopathic normal pressure hydrocephalus patients were included. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the concentrations of proteins. Results Increased concentrations of brevican, tenascin-C and tenascin-R in CSF correlated with unfavourable outcome, with stronger outcome prediction ability compared to other biomarkers of brain tissue injury. CSF brevican, tenascin-R and serum neurocan gradually decreased with time (p = 0.04, p = 0.008, p = 0.005, respectively), while serum tenascin-C (p = 0.01) increased. CSF concentrations of brevican, neurocan and tenascin-R (only in time point 3) after TBI were lower than in the idiopathic normal pressure hydrocephalus group (p < 0.0001, p < 0.0001, and p = 0.0008, respectively). In serum, tenascin-C concentration was higher and neurocan lower compared to healthy controls (p = 0.02 and p = 0.0009). Conclusions These findings indicate that levels of extracellular matrix proteins are associated with clinical outcome following TBI and may act as markers for different pathophysiology than currently used protein biomarkers.

Tenascin-C is a possible mediator between initial brain injury and vasospasm-related and -unrelated delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Tenascin-C (TNC), a matricellular protein, exerts diverse functions, including tissue remodeling and apoptosis, and is induced in cerebrospinal fluid (CSF) after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to examine the relationships among CSF TNC levels, initial brain injury, delayed cerebral ischemia (DCI), and vasospasm after SAH. METHODS: CSF TNC levels were measured in 30 patients with aneurysmal SAH of Fisher computed tomography (CT) group III who were treated microsurgically or endovascularly with CSF drainage within 24 h of SAH. Admission World Federation of Neurosurgical Societies (WFNS) grade was supposed to indicate the severity of initial brain injury. Cerebral vasospasm was defined as narrowed (≥ 25 %) cerebral arteries demonstrated by angiography. DCI was defined as any neurological deterioration presumed related to ischemia that persisted for ≥ 1 h. RESULTS: Higher CSF TNC levels were correlated with worse admission WFNS grades. Vasospasm was aggravated with higher TNC levels. DCI occurred regardless of the degree of vasospasm but was associated with TNC induction. Multivariate analyses showed that higher TNC levels and vasospasm were independent predictors of DCI occurrence. CONCLUSIONS: SAH (initial brain injury) that is more severe induces more TNC, which may cause the subsequent development of both vasospasm and vasospasm-unrelated secondary brain injury, leading to DCI.

Cerebrospinal fluid tenascin-C in cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Tenascin-C (TNC) has been reported to be a useful biomarker for the activity of inflammatory diseases. This study investigated the association between TNC levels in the cerebrospinal fluid (CSF) and symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (SAH), and the prognostic value of TNC levels. METHODS: TNC levels were measured in CSF in 33 consecutive patients diagnosed with aneurysmal SAH of Fisher computed tomography group III and were compared between those with and without subsequent cerebral vasospasm. Factors influencing symptomatic vasospasm were determined using multivariate logistic regression analyses. The receiver-operating characteristic curve technique was used to assess specificity and sensitivity in the prediction of symptomatic vasospasm. RESULTS: The CSF TNC levels peaked immediately after SAH and were significantly higher in patients who subsequently developed symptomatic vasospasm than in those who did not. On multivariate analyses, higher TNC levels in the CSF (odds ratio, 1.059; 95% confidence interval, 1.023-1.096; P<0.001) and World Federation of Neurosurgical Societies grades IV to V on admission (odds ratio, 3.238; 95% confidence interval, 1.033-10.152; P<0.05) significantly predicted symptomatic vasospasm. To predict the onset of symptomatic vasospasm, 16.2 ng/mL was considered as an appropriate cut-off value for CSF TNC on days 1 through 6, giving a sensitivity of 81.0% and a specificity of 79.5% (negative and positive predictive values: 82.3% and 76.7%, respectively). CONCLUSIONS: TNC in the CSF may be a useful biomarker for predicting subsequent development of cerebral vasospasm.

Cerebrospinal fluid tenascin-C increases preceding the development of chronic shunt-dependent hydrocephalus after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The possible cause of chronic hydrocephalus after subarachnoid hemorrhage (SAH) has been reported to be meningeal fibrosis. We examined whether the induction of tenascin-C (TN-C), an extracellular matrix glycoprotein known to promote tissue fibrosis, was associated with chronic hydrocephalus after SAH. METHODS: We prospectively measured cerebrospinal fluid TN-C levels in 7 control patients with unruptured cerebral aneurysms and in 29 consecutive patients with aneurysmal SAH on days 1 to 12. RESULTS: Cerebrospinal fluid TN-C levels were less than the diagnostic threshold level in control patients but markedly increased after SAH. Higher TN-C levels were observed in patients with more severe SAH on admission CT, ventricular drainage for acute obstructive hydrocephalus, and a worse outcome. Independent of these factors, however, cerebrospinal fluid TN-C levels were significantly higher in patients with than without subsequent chronic shunt-dependent hydrocephalus on days 1 to 9. CONCLUSIONS: These findings suggest the possible involvement of TN-C in the development of chronic hydrocephalus after SAH and encourage further studies.