CSF levels of a set of neurotrophic factors (brain-derived neurotrophic factor, nerve growth factor) and neuropeptides (neuropeptide Y, galanin) in epileptic children.

This paper aims to investigate the possible roles of a set of neurotrophic factors (brain-derived neurotrophic factor-BDNF, nerve growth factor-NGF) and neuropeptides (neuropeptide Y-NPY, and galanin) in children with active epileptogenesis. The cerebrospinal fluid (CSF) levels of BDNF, NPY, NGF and galanin were measured with enzyme-linked immunosorbent assays in epileptic children (n = 73) and controls (n = 64). There were no significant alterations in the CSF levels of BDNF, NPY and NGF in epileptic children with active clinical seizures compared with the levels of controls. However profoundly depressed galanin levels were found in infants with epileptic encephalopathy (mean ± SD:0.63 ± 0.19 pg/ml) and significantly increased galanin levels were measured in children with drug resistant epilepsy during the period of status epilepticus (mean ± SD: 6.92 ± 1.19, pg/ml pg/ml) compared with the levels of controls. Depressed levels of galanin might reflect a defective anti-epileptogenic effect of galanin in infants with epileptic encephalopathy. On the contrary, increased CSF levels of galanin might be a result of anti-epileptogenic effects of this peptide in epileptic children with status epilepticus.

The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy.

Our objective is to explore the effects of levetiracetam on the levels of neuropeptides, serum activity and concentrations of oxidative stress and inflammatory response proteins, and levels of brain injury marker in patients with refractory epilepsy. Seventy-two patients with refractory epilepsy received levetiracetam treatment. Neuropeptides galanin (GAL) and neuropeptide Y (NPY) in plasma and cerebrospinal fluid (CSF) were detected using double-antibody sandwich immunoassay and radioimmunoassay, respectively. Enzyme-linked immunosorbent assay was used to detect serum activity of paraoxonase (PON1) and serum concentrations of oxidized low-density lipoprotein (ox-LDL) and S100B. Arylesterase (ARE) activity was measured by colorimetric assay, and immune scatter turbidimetry was used to detect a high-sensitivity C-reactive protein (hs-CRP). After treatment, NPY and GAL in plasma and CSF of the patients were significantly decreased as compared to concentrations before treatment (P < 0.05). Levetiracetam reduced serum activities of PON1 and ARE (P < 0.05) and led to markedly increased serum levels of ox-LDL (P < 0.05). Serum concentrations of hs-CRP and S100B protein were significantly lower after levetiracetam administrations than before treatment (P < 0.05). Levetiracetam treatment had a clear beneficial effect on the overall quality of life (QOL) scores of the patients, as indicated by significantly improved cognitive functioning, behavior problems, emotional conditioning, physical condition, social functioning, self-assessed life quality score, self-assessed health score, and the total QOL score (P < 0.05). Levetiracetam can improve life quality of patients with refractory epilepsy, decrease NPY and GAL in plasma and cerebrospinal fluid, serum PON1 and ARE activities, and serum levels of ox-LDL, hs-CRP, and S100B. Levetiracetam therefore may be considered a drug of choice for treating refractory epilepsy.

Galanin and α-MSH autoantibodies in cerebrospinal fluid of patients with Alzheimer's disease.

BACKGROUND: Neuropeptides galanin and α-melanocyte-stimulating hormone (α-MSH) are involved in the regulation of memory and appetite. Increased galanin and decreased α-MSH levels were reported in postmortem brains of patients with Alzheimer's disease (AD) but the underlying mechanisms are uncertain. Here we studied if autoantibodies (autoAbs) reacting with galanin and α-MSH are altered in AD. METHODS: Levels of free and total IgG autoAbs reacting with galanin and α-MSH were measured in sera and cerebrospinal fluid (CSF) of 18 subjects with AD and in 15 age-matched non-demented controls. Values were correlated with Mini-Mental State Examination (MMSE) score, body mass index (BMI) and CSF levels of AD biomarkers. RESULTS: CSF levels of total but not free IgG autoAbs against galanin were increased in AD, resulting in increased percentage of galanin autoAbs present as immune complexes. CSF levels of galanin total autoAbs and α-MSH free autoAbs correlated negatively with the severity of cognitive impairment as measured by MMSE. Both total and free autoAbs against galanin and α-MSH in CSF correlated negatively with age in AD patients but not in controls. CSF levels of galanin autoAbs and free α-MSH AutoAbs negatively correlated with CSF levels of t-Tau, p-Tau and ratios of t-Tau/Aß42 or p-Tau/Aß42 in AD patients but not in controls. CONCLUSIONS: AutoAbs reacting with galanin and α-MSH are present in CSF and are associated with clinical characteristics of AD patients. The functional significance and therapeutic potential of these autoAbs should be further clarified.

CSF galanin and cognition after shunt surgery in normal pressure hydrocephalus.

BACKGROUND: "Normal" pressure hydrocephalus (NPH) is associated with injury to neurotransmitter and neuropeptide systems that recovers after surgery. This could be linked to changes in galanin, a neuropeptide with inhibitory effects on basal forebrain cognitive function. OBJECTIVE: To examine changes in CSF galanin concentrations in patients with normal pressure hydrocephalus undergoing shunt surgery, and to investigate the relation between these changes and cognitive functioning. METHODS: Eight patients underwent surgery for idiopathic normal pressure hydrocephalus. Lumbar CSF galanin determinations, cognitive status, and clinical status were quantified before operation and six months after. Cognition was assessed by an extensive battery of tests measuring attention, memory, speed of mental processing, visuospatial function, and frontal lobe function. RESULTS: CSF galanin concentration decreased after surgery. This reduction correlated with improved clinical and cognitive functioning, specifically with attention and visuomotor speed, visuoconstructive and frontal functioning, and clinical status according to the NPH scale, including the sphincter and cognitive components. CONCLUSIONS: The cognitive and clinical improvement after shunt implantation correlated with CSF galanin levels, suggesting that the distribution or function of this agent involves cerebral structures that have some potential for recovery. In this study, galanin was related to several cognitive functions that may be associated with the fronto-subcortical deficits underlying cognitive dysfunction in normal pressure hydrocephalus.

Could reduced cerebrospinal fluid (csf) galanin contribute to restricted eating in anorexia nervosa?

Galanin (GAL) and gamma amino butyric acid (GABA) are orexigenic neuropeptides that could contribute to the pathogenesis of anorexia nervosa (AN). To avoid the confounding effects of the ill state, we studied women who were recovered (> 1 year, normal weight, and regular menstrual cycles, no binging or purging) from AN (REC AN) and matched healthy control women (NC). CSF GAL was reduced in REC AN (64.4 +/- 8.6 pg/ml) compared to NC (72.0 +/- 11.6 pg/ml; p <.05), GABA was similar between groups. In the brain, GAL stimulates appetite and fat consumption. These data raise the question of whether alterations in brain GAL activity plays a role in clinical symptoms in AN, such as food restriction and fat avoidance.

Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre-treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY, NPY, SOM and GAL in the cerebrospinal fluid of patients with AD (n = 3), FTD (n = 3) and controls (n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states.

Metabolism of galanin and galanin (1-16) in isolated cerebrospinal fluid and spinal cord membranes from rat.

The occurrence of galanin (GAL) in the spinal cord and reports suggesting that it acts as an endogenous inhibitory spinal modulator in sensory/noxious transmission, have focused interest on its metabolism in the spinal cord. The metabolic half-lives and degradation patterns of GAL(1-29) and the high affinity N-terminal fragment GAL(1-16), were determined in isolated cerebrospinal fluid (CSF) from rats, and analysed by reverse phase HPLC. The half-lives for GAL(1-29) and GAL(1-16) in isolated rat CSF at 37 degrees C were 120 min and 60 min, respectively. The first degradation products which we could isolate and identify of GAL(1-16) were: GAL(3-16) and GAL(3-12) and for GAL(1-29): GAL(1-5) and GAL(1-4), all without affinity to spinal galanin receptors. Degradation studies of GAL(1-29) and GAL(1-16) in a spinal cord membrane preparation, in absence or presence of different protease inhibitors: E-64, pepstatin A, 3,4-DCI, bestatin, phosphoramidon, kelatorphan and thiorphan, or metal chelators: EDTA, EGTA and o-phenanthrolin, suggest that a phosphoramidon sensitive zinc-metalloprotease is mainly responsible for the degradation of GAL(1-29) and GAL(1-16), since both o-phenanthrolin (0.3 mM) and phosphoramidon (920 microM) substantially prolong their half-lives.