Brain-derived Neurotrophic Factor Levels In Cerebrospinal Fluid Research Articles

Brain-Derived Neurotrophic Factor (BDNF) Concentration Levels in Cerebrospinal Fluid and Plasma in Patients With Glioblastoma: A Prospective, Observational, Controlled Study.

Objective Glioblastomas (GBMs) are among the most frequent and most malignant of untreatable brain tumors. A GBM marker could accelerate diagnosis and facilitate therapeutic monitoring. This prospective, observational, controlled study compared brain-derived neurotrophic factor (BDNF) levels in cerebrospinal fluid (CSF) and plasma between patients with GBM and a control group. Materials and methods Patients in the observational group underwent elective GBM resection (n=24, 55.8%).Control patients (n=19, 44.2%) had elective brain surgery for an unrelated, non-neoplastic, non-traumatic pathology. We measured BDNF levels in tumors, CSF, and plasma with enzyme-linked immunosorbent assay (ELISA). Peripheral blood and CSF samples were collected before surgery, and tumors were sampled intraoperatively. We analyzed correlations between BDNF levels and patient sex, age, seizures, smoking, diabetes mellitus (DM), and the use of selected antiepileptic drug (AED) and antihypertensive drug groups. Results The mean CSF BDNF concentration was significantly lower in patients with GBM (6.5 pg/mL) than in controls (11.48 pg/mL) (p=0.002). Similarly, the mean plasma BDNF concentration was significantly lower in patients with GBM (288.59 pg/mL) than in controls (574.06 pg/mL) (p=0.0005). None of the examined factors influenced CSF, plasma, or tumor tissue BDNF concentrations (p>0.05). Conclusion Plasma and CSF BDNF levels were significantly lowerin adults with GBM than in controls. Thus, CSF and plasma BDNF levels may aid in GBM diagnoses. Further prospective studies are required.

BDNF and Pro-BDNF in Amyotrophic Lateral Sclerosis: A New Perspective for Biomarkers of Neurodegeneration.

Amyotrophic Lateral Sclerosis (ALS) is characterized by the progressive degeneration of upper or lower motor neurons, leading to muscle wasting and paralysis, resulting in respiratory failure and death. The precise ALS aetiology is poorly understood, mainly due to clinical and genetic heterogeneity. Thus, the identification of reliable biomarkers of disease could be helpful in clinical practice. In this study, we investigated whether the levels of brain-derived neurotrophic factor (BDNF) and its precursor Pro-BDNF in serum and cerebrospinal fluid (CSF) may reflect the pathological changes related to ALS. We found higher BDNF and lower Pro-BDNF levels in ALS sera compared to healthy controls. BDNF/Pro-BDNF ratio turned out to be accurate in distinguishing ALS patients from controls. Then, the correlations of these markers with several ALS clinical variables were evaluated. This analysis revealed three statistically significant associations: (1) Patients carrying the C9orf72 expansion significantly differed from non-carrier patients and showed serum BDNF levels comparable to control subjects; (2) BDNF levels in CSF were significantly higher in ALS patients with faster disease progression; (3) lower serum levels of Pro-BDNF were associated with a shorter survival. Therefore, we suggest that BDNF and Pro-BDNF, alone or in combination, might be used as ALS prognostic biomarkers.

Brain-Derived Neurotrophic Factor in the Cerebrospinal Fluid Increases During Electroconvulsive Therapy in Patients With Depression: A Preliminary Report.

Preclinical evidence suggests a role for brain-derived neurotrophic factor (BDNF) in the mode of action of electroconvulsive therapy (ECT). Clinical data regarding BDNF levels in serum or plasma are more inconsistent. We measured BDNF levels from the cerebrospinal fluid (CSF) in patients with major depression before and shortly after a course of ECT. Cerebrospinal fluid and serum BDNF levels were determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We included 9 patients with a severe depressive episode within a major depressive disorder into the study. The CSF BDNF concentrations at baseline were lower compared with those CSF BDNF levels after the complete ECT treatment (P = 0.042), whereas no such a constellation was found for serum BDNF. No associations between the BDNF levels and the amount of individual ECT sessions or the reduction of the depressive symptoms were found. For the first time, it has been shown that CSF BDNF concentrations increase during a course of ECT in patients with a severe unipolar depressive episode, which is in line with the neurotrophin hypothesis as a mode of action of ECT, although it was not possible to demonstrate either a dose-effect relation or a relationship with the actual antidepressant effects in our small sample. Major limitation is the small sample size.

Oral administration of BDNF and/or GDNF normalizes serum BDNF level in the olfactory bulbectomized rats: A proof of concept study

BackgroundNeurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier.MethodsAdult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid.ResultsA significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit.ConclusionThis study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated.

Changes in neurotrophic and inflammatory factors in the cerebrospinal fluid of patients with postherpetic neuralgia

Inflammatory and neurotrophic factors are involved in postherpetic neuralgia (PHN), but the association of these factors in the cerebrospinal fluid (CSF) with the level of pain is poorly known. The present study aimed to examine the changes in neurotrophic and inflammatory factors in the CSF of patients with PHN and to study the correlation between these factors and the degree of pain. Fifty patients with PHN and 28 patients with hemifacial spasm (as controls) were recruited between May 2015 and March 2016. CSF levels of inflammatory and neurotrophic factors were measured by ELISA. Compared with controls, patients with PHN had lower CSF levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin (NT)-3, NT-5, and P substance (all P<0.05), and higher CSF levels of interleukin (IL)-1β (P=0.050). Among patients with PHN, CSF BDNF levels were positively correlated to IL-8 (rs=0.229, P=0.04); glial cell line-derived neurotrophic factor (GDNF) levels to IL-8 (rs=0.326, P=0.004) levels; NGF levels to tumor necrosis factor (TNF)-α levels (rs=0.229, P=0.044); NT-3 levels to IL-1β (rs=0.228, P=0.045); and NT-5 levels to IL-8 (rs=0.388, P<0.001), and TNF-α (rs=0.445, P<0.001) levels. Inflammatory and neurotrophic factors were not correlated with the visual analog scale score and von Frey. Multivariable linear regression showed PHN was associated with NGF (P=0.038) and BDNF (P=0.029), independently from age and major medical history. In conclusion, patients with PHN showed low levels of BDNF, NGF, NT-3, and NT-5. Among patients with PHN, CSF levels of neurotrophic factors positively correlated with inflammatory factors.

Examination of neurological prognostic markers in patients with respiratory syncytial virus-associated encephalopathy

No biomarker has been established as a prognostic indicator of acute encephalopathy associated with various etiological factors. In this study, we examined useful prognostic biomarkers in patients with acute encephalopathy associated with respiratory syncytial virus (RSV) infection. The subjects were 11 children with RSV-associated encephalopathy admitted to our hospital. We measured the levels of interleukin (IL)-6, brain-derived neurotrophic factor (BDNF) and nitrogen oxide (NO)x in cerebrospinal fluid collected on the day of admission. Using the pediatric cerebral performance categories (PCPC) score as a prognostic indicator, we evaluated the association between the biomarkers and neurologic prognosis. Concerning neurologic prognosis, sequelae were noted in more than 50% of the subjects. There was no association between prognosis and age/sex. Increases in the levels of all biomarkers were observed in all subjects. IL-6 and BDNF levels were correlated with PCPC score, but not with NOx. Of the biomarkers investigated, the IL-6 and BDNF levels in cerebrospinal fluid were shown to be correlated with neurologic prognosis. Because many patients with this disease had severe sequelae, assessment should be conducted by early evaluation of the biomarkers examined in this study with respect to the clinical course.

Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury–Related Mortality

Background. Older adults have higher mortality rates after severe traumatic brain injury (TBI) compared to younger adults. Brain-derived neurotrophic factor (BDNF) signaling is altered in aging and is important to TBI given its role in neuronal survival/plasticity and autonomic function. Following experimental TBI, acute BDNF administration has not been efficacious. Clinically, genetic variation in BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) can be protective against acute mortality. Postacutely, these genotypes carry lower mortality risk in older adults and greater mortality risk among younger adults. Objective. Investigate BDNF levels in mortality/outcome following severe TBI in the context of age and genetic risk. Methods. Cerebrospinal fluid (CSF) and serum BDNF were assessed prospectively during the first week following severe TBI (n = 203) and in controls (n = 10). Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors. Results. CSF BDNF levels tended to be higher post-TBI (P = .061) versus controls and were associated with time until death (P = .042). In contrast, serum BDNF levels were reduced post-TBI versus controls (P < .0001). Both gene * BDNF serum and gene * age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI (P = .07). Conclusions. BDNF levels predicted mortality, in addition to gene * age interactions, suggesting levels capture additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to injury and age-related increases in pro-apoptotic BDNF target receptors. Negative CSF and serum BDNF correlations post-TBI suggest blood–brain barrier transit alterations. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment.

Reduced cerebrospinal fluid levels of brain-derived neurotrophic factor is associated with cognitive impairment in late-life major depression.

Late-life depression (LLD) is associated with reduced neurotrophic support and abnormalities in neurodegenerative cascades. The aim of the present study is to determine the concentrations of brain-derived neurotrophic factor (BDNF), amyloid-β42, total Tau, and phosphorylated Tau in the cerebrospinal fluid (CSF) of patients with LLD and cognitive impairment compared to healthy older adults. We included 25 antidepressant-free patients with LLD (10 with mild cognitive impairment [LLD + MCI] and 15 with no cognitive decline [LLD + NCD]) and 25 healthy older adults as a comparison group. Depressive symptoms were assessed by the 21-item Hamilton Depression Rating Scale (HDRS-21) and cognitive performance by a comprehensive cognitive battery. Patients with LLD + MCI showed significantly lower CSF BDNF levels compared to LLD + NCD and healthy controls (p = .003). There were no significant differences in Alzheimer's disease-related CSF biomarkers between groups. CSF BDNF concentrations were positively correlated with Cambridge Cognitive Test (CAMCOG) scores (r = .36, p = .02). The present study adds to the growing body of evidence that abnormalities in the BDNF system are involved in the pathophysiology of LLD. The reduction of the availability of BDNF in the central nervous system may indicate increased vulnerability to the development of several age-related neuropsychiatric disorders as well as to adverse cognitive outcomes.

Changes in HIF-1α, VEGF, NGF and BDNF levels in cerebrospinal fluid and their relationship with cognitive impairment in patients with cerebral infarction

This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=0.037 and P=0.000; P=0.023 and P=0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hypoxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.

Robust changes in expression of brain-derived neurotrophic factor (BDNF) mRNA and protein across the brain do not translate to detectable changes in BDNF levels in CSF or plasma

Adult rats were treated acutely with peripheral kainic acid (KA), and changes in brain-derived neurotrophic factor (BDNF) mRNA and protein were tracked over time across multiple brain regions. Despite robust elevation in both mRNA and protein in multiple brain regions, plasma BDNF was unchanged and cerebrospinal fluid (CSF) BDNF levels remained undetectable. Primary neurons were then treated with KA. BDNF was similarly elevated within neurons, but was undetectable in neuronal media. Thus, while deficits in BDNF signaling have been implicated in a number of diseases, these data suggest that extracellular concentrations of BDNF may not be a facile biomarker for changes in neurons.

Decreased BDNF levels in CSF of drug-naive first-episode psychotic subjects: correlation with plasma BDNF and psychopathology

Brain-derived neurotrophic factor (BDNF), which plays an important role in neurodevelopmental plasticity and cognitive performance, has been implicated in neuropsychopathology of schizophrenia. We examined the levels of both cerebrospinal fluid (CSF) and plasma BDNF concomitantly in drug-naive first-episode psychotic (FEP) subjects with ELISA to determine if these levels were different from control values and if any correlation exists between CSF and plasma BDNF levels. A significant reduction in BDNF protein levels was observed in both plasma and CSF of FEP subjects compared to controls. BDNF levels showed significant negative correlation with the scores of baseline PANSS positive symptom subscales. In addition, there was a significant positive correlation between plasma and CSF BDNF levels in FEP subjects. The parallel changes in BDNF levels in plasma and CSF indicate that plasma BDNF levels reflect the brain changes in BDNF levels in schizophrenia.