Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of alzheimer type and multi-infarct dementia
ABSTRACT Plasma and cerebrospinal fluid (CSF) from 20 patients with Alzheimer's dementia or senile dementia of Alzheimer type (AD/SDAT), 23 with multi-infarct dementia (MID) and 16 controls were assayed for their content of immunoglobulins (Ig) and albumin (Alb). The concentrations of IgG and Alb were used to analyze the blood-CSF barrier function in the respective group.MID patients had significantly (P < 0.001) elevated plasma IgG levels compared to controls and AD/SDAT patients. CSF concentration of Alb was significantly higher in MID (P < 0.01) and AD/SDAT (P < 0.05) patients compared to the controls. Concentration of CSF IgG was significantly (P < 0.05) lower in AD/SDAT patients compared to the MID patients; no significant differences were found when CSF concentrations of IgG of demented patients were compared to controls. These findings may indicate a blood-CSF barrier dysfunction especially in cases with MID with significantly (P < 0.001) elevated values of transudation. Also these findings indicate a non-specific and/or specific binding of IgG in CNS tissue and/or vessel walls in both forms of dementia on the basis of low IgG ratios compared to proportionally higher Alb ratios.There were no signs of local synthesis of IgG in CNS in either group of demented patients.
SourceAvailable from: Takashi D Y Kozai[Show abstract] [Hide abstract]
ABSTRACT: Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior, or to monitor patients' conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood-brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted CNS sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity.ACS Chemical Neuroscience 12/2014; · 4.21 Impact Factor
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ABSTRACT: Chronic implantation of microelectrodes into the cortex has been shown to lead to inflammatory gliosis and neuronal loss in the microenvironment immediately surrounding the probe, a hypothesized cause of neural recording failure. Caspase-1 (aka Interleukin 1β converting enzyme) is known to play a key role in both inflammation and programmed cell death, particularly in stroke and neurodegenerative diseases. Caspase-1 knockout (KO) mice are resistant to apoptosis and these mice have preserved neurologic function by reducing ischemia-induced brain injury in stroke models. Local ischemic injury can occur following neural probe insertion and thus in this study we investigated the hypothesis that caspase-1 KO mice would have less ischemic injury surrounding the neural probe. In this study, caspase-1 KO mice were implanted with chronic single shank 3 mm Michigan probes into V1m cortex. Electrophysiology recording showed significantly improved single-unit recording performance (yield and signal to noise ratio) of caspase-1 KO mice compared to wild type C57B6 (WT) mice over the course of up to 6 months for the majority of the depth. The higher yield is supported by the improved neuronal survival in the caspase-1 KO mice. Impedance fluctuates over time but appears to be steadier in the caspase-1 KO especially at longer time points, suggesting milder glia scarring. These findings show that caspase-1 is a promising target for pharmacologic interventions.Biomaterials 12/2014; 35(36):9620–9634. DOI:10.1016/j.biomaterials.2014.08.006 · 8.31 Impact Factor
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ABSTRACT: Backgrounds: The pathogenesis of cerebral white matter hyperintensities (WMH) has been poorly understood. Our aim was to investigate the association of circulating proteins, the biomarkers of inflammation, blood-brain barrier (BBB) dysfunction, and thrombosis with WMH in non-stroke individuals. Methods: Demographic, laboratory, and brain magnetic resonance imaging parameters were prospectively analyzed in 137 subjects. The relationship between plasma interleukin-6, tumor necrosis factor-α, matrx-metalloproteinase-9 (MMP-9), plasminogen activator inhibitor-1 and overt WMH (Fazekas grading score ≥2) was analyzed. Results: In univariate analysis, old age, high blood pressure, history of hypertension, and elevated plasma MMP-9 level were associated with overt WMH. In multivariate analysis, plasma MMP-9 still maintained a significant association with WMH. Plasma MMP-9 level was weakly but significantly associated with WMH volume (r = 0.232, p = 0.006). All the other circulating proteins examined failed to demonstrate a significant relationship with WMH. Conclusions: Plasma MMP-9 is associated with pathophysiology of WMH development. © 2014 S. Karger AG, Basel.European Neurology 09/2014; 72(3-4):234-240. DOI:10.1159/000362876 · 1.36 Impact Factor