Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Pisani, Valerio; Stefani, Alessandro; Pierantozzi, Mariangela; Natoli, Silvia; Stanzione, Paolo; Franciotta, Diego; Pisani, Antonio

doi:10.1186/1742-2094-9-188

Cited by 121 publications

(87 citation statements)

References 19 publications

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“…5,6 There is evidence for BBB hyperpermeability in PD by cerebrospinal fluid analysis and positron-emission tomography imaging but immunohistochemical proof remains elusive. 7,8 In the present study, we have used classic histologic staining and immunohistochemical techniques to examine BBB integrity in a postmortem study of the striata of a well-characterized cohort of PD patients and controls. The results are discussed in the context of an alternative model for the pathogenesis of PD.…”

Section: Introductionmentioning

confidence: 99%

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Gray

Woulfe

2015

J Cereb Blood Flow Metab

289

222

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In vivo studies have shown that blood-brain barrier (BBB) dysfunction is involved in the course of Parkinson's disease (PD). However, these have lacked either anatomic definition or the ability to recognize minute changes in BBB integrity. Here, using histologic markers of serum protein, iron, and erythrocyte extravasation, we have shown significantly increased permeability of the BBB in the postcommissural putamen of PD patients. The dense innervation of the striatum by PD-affected regions allows for exploitation of this permeability for therapeutic goals. These results are also discussed in the context of the retrograde transsynaptic hypothesis of PD spread. Keywords: α-synuclein; blood-brain barrier; Parkinson's disease; striatum INTRODUCTION Parkinson's disease (PD) is characterized by aggregation of filamentous or oligomerized α-synuclein and degeneration of specific neuronal regions. According to the dual-hit hypothesis of PD pathogenesis, a microbial or toxic pathogen within the gut lumen and the olfactory mucosa represents the pathogenic agent, with subsequent prion-like spread of pathology, first to the dorsal motor nucleus of the vagus and central olfactory areas, respectively, then to higher centers. The connectional anatomy linking the dorsal motor nucleus and olfactory bulb with higher centers such as the substantia nigra is unproven.We have previously proposed that disease could be spread hematogenously. 1 This is conceivable within the paradigm of retrograde (axon terminal to soma) Lewy pathology spread. 2,3 Almost all regions affected in Braak stage 1 have axon terminals outside the blood-brain barrier (BBB). That same BBB, however, protects the higher-order regions, whose axon terminals reside within the central nervous system, from blood-borne substances. Cell-to-cell spread is a potential mechanism to circumvent this protection but the connectional neuroanatomy is not consistent with the temporal order of Lewy pathology development as it is currently understood.Nigrostriatal dopaminergic neuronal cell bodies develop significant Lewy pathology, but recent studies strongly suggest that α-synuclein aggregation in these cells begins at presynaptic axon terminal in the striatum and spreads retrogradely to nigral

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Section: Introductionmentioning

confidence: 99%

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Gray

Woulfe

2015

J Cereb Blood Flow Metab

289

222

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“…This indicates possible dysfunction of the BBB (and/or blood-CSF-barrier) in PD progression. 151 Tight junctions. In a intracerebral rotenone model of PD in rats, using fluorescein as tight junctional BBB permeability marker, no changes were detected.…”

Section: Bbb In Parkinson's Diseasementioning

confidence: 99%

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Erdő

Dénès

Lange

2016

J Cereb Blood Flow Metab

328

260

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The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years. This article gives an overview on the major elements of the blood-brain barrier and its supporting mechanisms and also on their alterations during development, physiological aging process and age-associated neurodegenerative disorders (Alzheimer's disease, multiple sclerosis, Parkinson's disease, pharmacoresistant epilepsy). Besides the morphological alterations of the cellular elements (endothelial cells, astrocytes, pericytes, microglia, neuronal elements) of the BBB and neurovascular unit, the changes of the barrier at molecular level (tight junction proteins, adheres junction proteins, membrane transporters, basal lamina, extracellular matrix) are also summarized. The recognition of new players and initiators of the process of neurodegeneration at the level of the BBB may offer new avenues for novel therapeutic approaches for the treatment of numerous chronic neurodegenerative disorders currently without effective medication. KeywordsAging, blood-brain barrier, endothelial cells, neurodegenerative disorders, transport systems Structure of the blood-brain barrier (BBB)Homeostasis of the extracellular microenvironment in the neural tissue of the brain as well as its protection against neurotoxic compounds and variations in the composition of the blood are important for normal function of the neurons. It is warranted by a structure formed between blood and brain, which is therefore called the BBB.1 Clear evidence for the existence of this permeability barrier in the brain emerged in 1909 with the demonstration by Edwin Goldman (a South African-German) that a dye injected into the blood stream of a rat stained the whole body -except for the brain and spinal cord. The opposite was also true: injection of the dye into the cerebral ventricles stained the brain and spinal cord but not the rest of the body. 2,3 This occurs because most organs of the body are perfused by capillaries lined with endothelial cells (ECs) that have small pores (fenestrations) to allow for the rapid movement of small molecules into the organ interstitial fluid from the circulation. However, the capillary endothelium of the brain and spinal cord lack these pores because the ECs of brain capillary are connected to each other by continuous tight junctions (TJs), produced by the interaction of several transmembrane proteins that project into and seal the paracellular pathway.3-5 The interaction of these junctional proteins effectively blocks the free diffusion of

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“…In a recent study by Pisani and coauthors [59] it was shown that both albumin (Fig. 1A) and IgG (Fig.…”

Section: An Exemplary Angle Of Vision: Extra-pyramidal Syndromesmentioning

confidence: 79%

Strength and Weaknesses of Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease and Possible Detection of Overlaps with Frailty Process

Olivola¹,

Bassi²,

Pisani³

et al. 2013

CNSNDDT

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With the increase of human lifespan and refinement of diagnostic techniques dementia, and Alzheimer's disease (AD) in particular, have become a multi-decade process with a complex pathogenesis. The prognosis of AD patients, especially in late stages, may be strongly influenced by factors that go far beyond the well-recognized cascades (tau deposition, amyloid plaques). In this context, AD and Frailty, a multidimensional process of the elderly, inevitably overlap. Not surprisingly, the routine biomarkers collectable in the cerebrospinal fluid, while highly relevant in allowing specific diagnoses, becoming limiting when used to define severity and rate of progression of cognitive impairment. In reviewing merits and pitfalls of routine cerebrospinal fluid profile for AD, this manuscript will examine the state-of-theart related to a parallel field, the extrapyramidal disorders. For synucleinopathies, we will discuss the possibility to detect factors directly involved in earliest disease pathology (alpha-synuclein, tau-proteins) together with indexes of disease progression (i.e. dopamine-metabolite ratio and loss of blood-brain barrier integrity). This approach might guarantee the capability of monitoring putative disease-modifying strategies. However, we will show the likelihood that nonconventional approaches already proposed for Frail subjects (such as exercise-mediated neuro-protection) might prove to be a useful aid for an ageing brain already impaired by AD alterations. A crucial test for these hypotheses would be to apply this sort of interventional, and not merely pharmacological, therapy to homogeneous patient cohorts.

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Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Cited by 121 publications

References 19 publications

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Strength and Weaknesses of Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease and Possible Detection of Overlaps with Frailty Process

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Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Cited by 121 publications

References 19 publications

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Strength and Weaknesses of Cerebrospinal Fluid Biomarkers in Alzheimer&#8217;s Disease and Possible Detection of Overlaps with Frailty Process

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Strength and Weaknesses of Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease and Possible Detection of Overlaps with Frailty Process