Melatonin ameliorates blood–brain barrier permeability, glutathione, and nitric oxide levels in the choroid plexus of the infantile rats with kaolin-induced hydrocephalus

Turğut, Mehmet; Erdoğan, Serpil; Ergin, Kemal; Serter, Mukadder

doi:10.1016/j.brainres.2007.07.056

Cited by 31 publications

(20 citation statements)

References 31 publications

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“…Future work is required to examine this hypothesis as well as to evaluate the function and stability of the choroid plexus and arachnoid membrane in post-mortem and imaging studies in schizophrenia. Results from studies in the fields of stroke, brain injury and liver failure, have shown that such compounds as melatonin, idazoxan, an imidazoline 2 receptor ligand, and inhibitors of matrix metalloproteinases may protect against blood-brain barrier and choroid plexus pathologies induced by a variety of methods in cell culture experiments and rodent models (Chen et al, 2013; Turgut et al, 2007; Verma et al, 2010; Wang et al, 2014). Thus, based on this work, therapies aimed to remove the antigenic source and to normalize endothelial barrier functions may be applicable treatment modalities to explore for safety and efficacy trials in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Severance¹,

Gressitt²,

Alaedini³

et al. 2015

Brain, Behavior, and Immunity

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Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R2=0.34–0.55, p≤0.0001; controls R2=0.05–0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p≤0.001–0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature.

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Section: Discussionmentioning

confidence: 99%

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Severance¹,

Gressitt²,

Alaedini³

et al. 2015

Brain, Behavior, and Immunity

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show abstract

“…The absence of such a change in hydrocephalic rats further supports the idea that generalized BBB dysfunction is not a major phenomenon. One group claimed that detection of Tc99-diethylenetriamine penta-acetate DTPA in brain using a gamma camera following intravenous injection of the tracer into hydrocephalic rats was evidence of BBB breakdown [50]; however, only a single animal was used in each group and therefore the data cannot be considered credible. Increased levels of S-100 protein (20 kDa) in blood plasma of children with hydrocephalus were claimed to be indicative of BBB disruption [51]; however, this just as likely represents absorption of released S-100 through conventional CSF absorption routes.…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus

Bigio

Slobodian

Schellenberg

et al. 2011

Fluids Barriers CNS

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BackgroundHydrocephalus is associated with enlargement of cerebral ventricles. We hypothesized that magnetic resonance (MR) imaging parameters known to be influenced by tissue water content would change in parallel with ventricle size in young rats and that changes in blood-brain barrier (BBB) permeability would be detected.MethodsHydrocephalus was induced by injection of kaolin into the cisterna magna of 4-week-old rats, which were studied 1 or 3 weeks later. MR was used to measure longitudinal and transverse relaxation times (T1 and T2) and apparent diffusion coefficients in several regions. Brain tissue water content was measured by the wet-dry weight method, and tissue density was measured in Percoll gradient columns. BBB permeability was measured by quantitative imaging of changes on T1-weighted images following injection of gadolinium diethylenetriamine penta-acetate (Gd-DTPA) tracer and microscopically by detection of fluorescent dextran conjugates.ResultsIn nonhydrocephalic rats, water content decreased progressively from age 3 to 7 weeks. T1 and T2 and apparent diffusion coefficients did not exhibit parallel changes and there was no evidence of BBB permeability to tracers. The cerebral ventricles enlarged progressively in the weeks following kaolin injection. In hydrocephalic rats, the dorsal cortex was more dense and the white matter less so, indicating that the increased water content was largely confined to white matter. Hydrocephalus was associated with transient elevation of T1 in gray and white matter and persistent elevation of T2 in white matter. Changes in the apparent diffusion coefficients were significant only in white matter. Ventricle size correlated significantly with dorsal water content, T1, T2, and apparent diffusion coefficients. MR imaging showed evidence of Gd-DTPA leakage in periventricular tissue foci but not diffusely. These correlated with microscopic leak of larger dextran tracers.ConclusionsMR characteristics cannot be used as direct surrogates for water content in the immature rat model of hydrocephalus, probably because they are also influenced by other changes in tissue composition that occur during brain maturation. There is no evidence for widespread persistent opening of BBB as a consequence of hydrocephalus in young rats. However, increase in focal BBB permeability suggests that periventricular blood vessels may be disrupted.

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“…It is worth mentioning, however, that BBB permeability is not constant, but depends on the physiological state of animals. It was previously found that BBB permeability could be affected by the level of gonadal steroids (Wilson et al, 2008), melatonin (Turgut et al, 2007), and stress (Esposito et al, 2001). So it can be speculated that the varied results on the ability of LPS to cross the BBB could be, at least partially, caused by the different physiological states of the animals used in those studies.…”

Section: Discussionmentioning

confidence: 99%

Immune stress up regulates <i>TLR4</i> and <i>Tollip</i> gene expression in the hypothalamus of ewes

Herman¹,

Haziak²,

Tomaszewska-Zaremba³

2013

J. Anim. Feed Sci.

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Melatonin ameliorates blood–brain barrier permeability, glutathione, and nitric oxide levels in the choroid plexus of the infantile rats with kaolin-induced hydrocephalus

Cited by 31 publications

References 31 publications

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus

Immune stress up regulates <i>TLR4</i> and <i>Tollip</i> gene expression in the hypothalamus of ewes

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