scholarly journals Striatal Injury with 6-OHDA Transiently Increases Cerebrospinal GFAP and S100B

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Cristiane Batassini ◽  
Núbia Broetto ◽  
Lucas Silva Tortorelli ◽  
Milene Borsoi ◽  
Caroline Zanotto ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neuronal Damage ◽  
Time Frame ◽  
Current Data ◽  
Rotational Behaviour ◽  
Dopaminergic Pathway ◽  
Glial Changes ◽  
Striatal Injury ◽  
S100b Secretion ◽  
Intrastriatal Injection

Both glial fibrillary acidic protein (GFAP) and S100B have been used as markers of astroglial plasticity, particularly in brain injury; however, they do not necessarily change in the same time frame or direction. Herein, we induced a Parkinson’s disease (PD) model via a 6-OHDA intrastriatal injection in rats and investigated the changes in GFAP and S100B using ELISA in the substantia nigra (SN), striatum, and cerebrospinal fluid on the 1st, 7th, and 21st days following the injection. The model was validated using measurements of rotational behaviour induced by methylphenidate and tyrosine hydroxylase in the dopaminergic pathway. To our knowledge, this is the first measurement of cerebrospinal fluid S100B and GFAP in the 6-OHDA model of PD. Gliosis (based on a GFAP increase) was identified in the striatum, but not in the SN. We identified a transitory increment of cerebrospinal fluid S100B and GFAP on the 1st and 7th days, respectively. This initial change in cerebrospinal fluid S100B was apparently related to the mechanical lesion. However, the 6-OHDA-induced S100B secretion was confirmed in astrocyte cultures. Current data reinforce the idea that glial changes precede neuronal damage in PD; however, these findings also indicate that caution is necessary regarding the interpretation of data in this PD model.

scholarly journals Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer’s Disease Pathology and Neuronal Damage

2018 ◽  
Vol 62 (1) ◽  
pp. 385-397 ◽  
Author(s):  
Brianne M. Bettcher ◽  
Sterling C. Johnson ◽  
Ryan Fitch ◽  
Kaitlin B. Casaletto ◽  
Kate S. Heffernan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Plasma Levels ◽  
Neuronal Damage

scholarly journals Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer’s Disease

2020 ◽  
Vol 21 (17) ◽  
pp. 6298
Author(s):  
Petar Podlesniy ◽  
Franc Llorens ◽  
Margalida Puigròs ◽  
Nuria Serra ◽  
Diego Sepúlveda-Falla ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Mitochondrial Dna ◽  
Clinical Diagnosis ◽  
Neuronal Damage ◽  
Clinical Signs ◽  
Amyloid Peptide ◽  
Slow Progression ◽  
Csf Levels ◽  
T Tau ◽  
The Relationship

Alzheimer’s type dementia (AD) exhibits clinical heterogeneity, as well as differences in disease progression, as a subset of patients with a clinical diagnosis of AD progresses more rapidly (rpAD) than the typical AD of slow progression (spAD). Previous findings indicate that low cerebrospinal fluid (CSF) content of cell-free mitochondrial DNA (cf-mtDNA) precedes clinical signs of AD. We have now investigated the relationship between cf-mtDNA and other biomarkers of AD to determine whether a particular biomarker profile underlies the different rates of AD progression. We measured the content of cf-mtDNA, beta-amyloid peptide 1–42 (Aβ), total tau protein (t-tau) and phosphorylated tau (p-tau) in the CSF from a cohort of 95 subjects consisting of 49 controls with a neurologic disorder without dementia, 30 patients with a clinical diagnosis of spAD and 16 patients with rpAD. We found that 37% of controls met at least one AD biomarker criteria, while 53% and 44% of subjects with spAD and rpAD, respectively, did not fulfill the two core AD biomarker criteria: high t-tau and low Aβ in CSF. In the whole cohort, patients with spAD, but not with rpAD, showed a statistically significant 44% decrease of cf-mtDNA in CSF compared to control. When the cohort included only subjects selected by Aβ and t-tau biomarker criteria, the spAD group showed a larger decrease of cf-mtDNA (69%), whereas in the rpAD group cf-mtDNA levels remained unaltered. In the whole cohort, the CSF levels of cf-mtDNA correlated positively with Aβ and negatively with p-tau. Moreover, the ratio between cf-mtDNA and p-tau increased the sensitivity and specificity of spAD diagnosis up to 93% and 94%, respectively, in the biomarker-selected cohort. These results show that the content of cf-mtDNA in CSF correlates with the earliest pathological markers of the disease, Aβ and p-tau, but not with the marker of neuronal damage t-tau. Moreover, these findings confirm that low CSF content of cf-mtDNA is a biomarker for the early detection of AD and support the hypothesis that low cf-mtDNA, together with low Aβ and high p-tau, constitute a distinctive CSF biomarker profile that differentiates spAD from other neurological disorders.

scholarly journals Decreased Cerebrospinal Fluid Orexin-A (Hypocretin-1) Concentrations in Patients after Generalized Convulsive Status Epilepticus

2020 ◽  
Vol 9 (10) ◽  
pp. 3354
Author(s):  
Mojdeh Samzadeh ◽  
Ewa Papuć ◽  
Marzena Furtak-Niczyporuk ◽  
Konrad Rejdak
Keyword(s):  
Cerebrospinal Fluid ◽  
Status Epilepticus ◽  
Neuronal Damage ◽  
Study Groups ◽  
Convulsive Status Epilepticus ◽  
Orexin A ◽  
Diagnostic Lumbar Puncture ◽  
Turn Over ◽  
Hypocretin 1

The effects of status epilepticus on the orexin/hypocretin system have yet to be investigated. The present study aimed to assay orexin-A/hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized convulsive status epilepticus (GCSE). The study groups included 20 GCSE patients, 24 patients diagnosed with epilepsy but remaining in remission (ER), and 25 normal controls (CTR). Diagnostic lumbar puncture was performed in GCSE patients within 3–10 days of seizure cessation, as well as in the ER and to CTR subjects. Among all GCSE patients, the outcome was graded according to the modified Rankin Scale (mRS) at 1-month follow-up. Orexin-A levels were measured in unextracted CSF samples, using a commercial radioimmunoassay. There was a significant overall difference in median CSF orexin-A concentrations between GCSE, RE, and CTR patients (p < 0.001). The lowest concentrations were noted in the GCSE group compared to ER (p < 0.001) or CTR (p < 0.001). CSF orexin-A levels in GCSE patients inversely correlated with clinical outcome as assessed on the mRS at 1-month follow-up (r = −0.55; p = 0.1). In conclusion, CSF orexin-A levels may serve as a biomarker of increased turn-over of the peptide or post-SE neuronal damage, and implicates the orexin system in the pathogenesis of SE.

scholarly journals Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ngoc Dung Le ◽  
Lukas Muri ◽  
Denis Grandgirard ◽  
Jens Kuhle ◽  
David Leppert ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Light Chain ◽  
Pneumococcal Meningitis ◽  
Neuronal Damage ◽  
Neuronal Injury ◽  
Health Concern ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Inflammatory Phase

Abstract Background Pneumococcal meningitis (PM) remains a global public health concern and affects all age groups. If acquired during infancy or childhood, permanent neurofunctional deficits including cognitive impairment, cerebral palsy, and secondary epilepsy are typical sequelae of neuronal injury. Determination of patients at risk for the development of brain injury and subsequent neurofunctional sequelae could help to identify patients for focused management. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released upon neuronal injury into the cerebrospinal fluid (CSF) and blood. As little is known about the course of neurofilament release in the course of PM, we measured CSF and serum NfL levels longitudinally in experimental PM (ePM). Methods Eleven-day-old infant Wistar rats were infected intracisternally with Streptococcus pneumoniae and treated with ceftriaxone. At 18 and 42 h post-infection (hpi), the blood and CSF were sampled for NfL measurements by a single molecule array technology. Inflammatory cytokines and MMP-9 in CSF were quantified by magnetic bead multiplex assay (Luminex®) and by gel zymography, respectively. Results In ePM, CSF and serum NfL levels started to increase at 18 hpi and were 26- and 3.5-fold increased, respectively, compared to mock-infected animals at 42 hpi (p < 0.0001). CSF and serum NfL correlated at 18 hpi (p < 0.05, r = 0.4716) and 42 hpi (p < 0.0001, r = 0.8179). Both CSF and serum NfL at 42 hpi strongly correlated with CSF levels of IL-1β, TNF-α, and IL-6 and of MMP-9 depending on their individual kinetics. Conclusion Current results demonstrate that during the peak inflammatory phase of ePM, NfL levels in CSF and serum are the highest among CNS disease models studied so far. Given the strong correlation of CSF versus serum NfL, and its CNS-specific signal character, longitudinal measurements to monitor the course of PM could be performed based on blood sample tests, i.e., without the need of repetitive spinal taps. We conclude that NfL in the serum should be evaluated as a biomarker in PM.

Cerebrospinal fluid ubiquitin C-terminal hydrolase as a novel marker of neuronal damage after epileptic seizure

2013 ◽  
Vol 103 (2-3) ◽  
pp. 205-210 ◽  
Author(s):  
Yajun Li ◽  
Zhenghai Wang ◽  
Bei Zhang ◽  
Xiao Zhe ◽  
Mingjue Wang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Epileptic Seizure ◽  
Neuronal Damage

scholarly journals Unchanged Survival Rates of 14-3-3γ Knockout Mice after Inoculation with Pathological Prion Protein

2005 ◽  
Vol 25 (4) ◽  
pp. 1339-1346 ◽  
Author(s):  
Petra Steinacker ◽  
Petra Schwarz ◽  
Kerstin Reim ◽  
Peter Brechlin ◽  
Olaf Jahn ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Western Blot ◽  
Neuronal Damage ◽  
Survival Rates ◽  
Rocky Mountain ◽  
Laboratory Strain ◽  
Clinical Findings ◽  
Jakob Disease ◽  
Mutant Mouse Line

ABSTRACT The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) is based on typical clinical findings and is supported by a positive 14-3-3 Western blot of cerebrospinal fluid. However, it is not clear whether 14-3-3 indicates general neuronal damage or is of pathophysiological relevance in CJD. The fact that the 14-3-3 isoform spectrum in cerebrospinal fluid does not correspond to that found in the brain points to a regulated process. To investigate a possible role of 14-3-3 proteins in transmissible spongiform diseases, we generated a 14-3-3γ-deficient mutant mouse line by using a classical knockout strategy. The anatomy and cage behavior of the mutant mice were normal. Western blot analyses of brain homogenates revealed no changes in the protein expression of other 14-3-3 isoforms (ε, β, ζ, and η). Proteomic analyses of mouse brains by two-dimensional differential gel electrophoresis showed that several proteins, including growth hormone, 1-Cys peroxiredoxin, CCT-zeta, glucose-6-phosphate isomerase, GRP170 precursor, and α-SNAP, were differentially expressed. Mutant and wild-type mice were inoculated either intracerebrally or intraperitoneally with the Rocky Mountain Laboratory strain of scrapie, but no differences were detected in the postinoculation survival rates. These results indicate that 14-3-3γ is unlikely to play a causal role in CJD and related diseases.

scholarly journals Efavirenz and Metabolites in Cerebrospinal Fluid: Relationship withCYP2B6c.516G→T Genotype and Perturbed Blood-Brain Barrier Due to Tuberculous Meningitis

2016 ◽  
Vol 60 (8) ◽  
pp. 4511-4518 ◽  
Author(s):  
Sam Nightingale ◽  
Tran Thi Hong Chau ◽  
Martin Fisher ◽  
Mark Nelson ◽  
Alan Winston ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Neuronal Damage ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Toxic Concentration ◽  
Metabolite Concentrations ◽  
Blood Brain Barrier Integrity

ABSTRACTEfavirenz (EFZ) has been associated with neuropsychiatric side effects. Recently, the 8-hydroxy-EFZ (8OH-EFZ) metabolite has been shown to be a potent neurotoxinin vitro, inducing neuronal damage at concentrations of 3.3 ng/ml. EFZ induced similar neuronal damage at concentrations of 31.6 ng/ml. We investigated the effect of genotype and blood-brain barrier integrity on EFZ metabolite concentrations in cerebrospinal fluid (CSF). We measured CSF drug concentrations in subjects from two separate study populations: 47 subjects with tuberculous meningitis (TBM) coinfection in Vietnam receiving 800 mg EFZ with standard antituberculous treatment and 25 subjects from the PARTITION study in the United Kingdom without central nervous system infection receiving 600 mg EFZ. EFZ and metabolite concentrations in CSF and plasma were measured and compared with estimates of effectiveness and neurotoxicity from available publishedin vitroandin vivodata. The effect of theCYP2B6c.516G→T genotype (GG genotype, fast EFV metabolizer status; GT genotype, intermediate EFV metabolizer status; TT genotype, slow EFV metabolizer status) was examined. The mean CSF concentrations of EFZ and 8OH-EFZ in the TBM group were 60.3 and 39.3 ng/ml, respectively, and those in the no-TBM group were 15.0 and 5.9 ng/ml, respectively. Plasma EFZ and 8OH-EFZ concentrations were similar between the two groups. CSF EFZ concentrations were above thein vitrotoxic concentration in 76% of samples (GG genotype, 61%; GT genotype, 90%; TT genotype, 100%) in the TBM group and 13% of samples (GG genotype, 0%; GT genotype, 18%; TT genotype, 50%) in the no-TBM group. CSF 8OH-EFZ concentrations were above thein vitrotoxic concentration in 98% of the TBM group and 87% of the no-TBM group; levels were independent of genotype but correlated with the CSF/plasma albumin ratio. Potentially neurotoxic concentrations of 8OH-EFZ are frequently observed in CSF independently of theCYP2B6genotype, particularly in those with impaired blood-brain barrier integrity.

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