Re: Ag+ and blood/brain barrier (fwd)

["Ronald F. Vetter" <rfvetter@xxxxxxxxxxxxxxxx>]

>Posted-Date: Mon, 13 May 1996 15:20:09 -0700
>Date: Mon, 13 May 1996 15:19:34 -0700 (PDT)
>From: Camilla Cracchiolo <camilla@xxxxxxxxxxxx>
>To: "Ronald F. Vetter" <rfvetter@xxxxxxxxxxxxxxxx>
>Subject: Re: Ag+ and blood/brain barrier (fwd)
Here are some abstracts passed on to me.  You might find them interesting.
I, Ron,  thank:  Camilla Cracchiolo, RN   camilla@xxxxxxxxxxxx

Here are reports of two women with argyria (silver poisoning) with
demonstrable silver in the CNS. Silver crosses the BBB in rodents and is
apparently neurotoxic. These references indicate that humans are probably
no different. Prior to modern antibiotics, silver (as well as other heavy
metals like arsenic and mercury) were used as antimicrobials. Perhaps the
older literature has some discussions of the neurotoxicity of silver
treatments.

Dietl HW.  Anzil AP.  Mehraein P. Brain involvement in generalized
argyria. Clinical Neuropathology.  3(1):32-6, 1984 Jan-Feb.
   Abstract
    Cutaneous argyria was diagnosed in a 59-year-old woman. Manic depressive
    psychosis developed at about the same or a short time thereafter. The
    patient died 6 years later from a ruptured aortic aneurysm. At autopsy
    silver deposits were seen in skin, mucous membranes, heart, kidney, and
    liver. In the central nervous system the leptomeninges and choroid
    plexuses contained silver granules. In addition, silver granules were
    visualized in the walls of many intraparenchymal vessels, particularly of
    the basal ganglia, hypothalamus, substantia nigra, and cerebellum.
    Progressive glial changes and cellular gliosis were evident in many areas
    of the brain. With the electron microscope the deposition of silver
    granules in basal membrane structures of the choroid plexus and
    intracerebral vasculature was amply confirmed. Furthermore, silver
    deposition was seen in brain parenchymal cells inside bodies of apparently
    lysosomal nature. The silver content of various brain regions was
    determined by absorption spectrophotometry.

Landas S.  Fischer J.  Wilkin LD.  Mitchell LD.  Johnson AK.  Turner JW.
Theriac M.  Moore KC. Demonstration of regional blood-brain barrier
permeability in human brain. Neuroscience Letters.  57(3):251-6, 1985 Jun
24.
   Abstract
    The brain of a 78-year-old woman with argyria was examined at autopsy.
    Silver nitrate deposition was observed in circumventricular organs (CVO)
    and in the paraventricular and supraoptic nuclei of the hypothalamus.
    These findings parallel animal experiments of other investigators and are
    the best demonstration so far of regional absence of the blood-brain
    barrier in humans. These observations demonstrate similarities between
    humans and other mammals of CVO anatomy, permeability to blood-borne
    agents, and perhaps neural connections between CVOs and magnocellular
    nuclei.

Rungby J.  Slomianka L.  Danscher G.  Andersen AH.  West MJ. A
quantitative evaluation of the neurotoxic effect of silver on the volumes
of the components of the developing rat hippocampus. Toxicology.
43(3):261-8, 1987 Mar.
   Abstract
    The volumes of the components of the hippocampus of rats subjected to
    subcutaneous injections of silver during the first 4 postnatal weeks were
    compared to those of littermate controls. Of the 14 components measured,
    only the pyramidal cell layer was found to be significantly smaller in the
    treated animals. These findings indicate that the perikaria of the
    pyramidal cells are either the first elements in the developing
    hippocampus to show signs of silver toxicity or that they are the
    selective sites of silver neurotoxicity. The volumetric approach is shown
    to be a sensitive means by which small localized neurotoxic effects can be
    detected.

Rungby J.  Danscher G. Hypoactivity in silver exposed mice. Acta
Pharmacologica et Toxicologica.  55(5):398-401, 1984 Nov.
   Abstract
    The functional implications of the presence of silver in the central
    nervous system are unknown. Since silver is present in the environment and
    since systemic silver poisoning leads to intraneuronal accumulations of
    the metal we have evaluated the possible effects of silver on the open
    field behaviour of mice. Argyric mice have been compared with controls in
    three experiments, one including long term administration of 0.015% silver
    nitrate in the drinking water and two in which the reactions of male and
    female mice to shock doses of silver lactate have been studied. In all
    experiments the silver treated mice were hypoactive. We suggest that this
    hypoactivity is due to an influence of silver upon the functional status
    of the CNS.

Rungby J.  Danscher G. Localization of exogenous silver in brain and
spinal cord of silver exposed rats. Acta Neuropathologica.  60(1-2):92-8,
1983.
   Abstract
    Exogenous silver in brain and spinal cord sections from rats treated with
    Protargol, silver lactate or silver nitrate was visualized by physical
    development. The silver penetrated the blood-brain barrier and accumulated
    in neurones and glia. The distribution of silver in the CNS was
    heterogeneous. Even with low doses and short survival periods, silver was
    found to accumulate in large motoneurones in the brain stem and spinal
    cord and neurones in the cerebellar nuclei. Silver was only found in di-
    and telencephalic structures after extensive exposure. Silver distribution
    following oral silver lactate and silver nitrate treatment differed in
    that silver nitrate resulted in a relatively high content of silver in
    glia whereas deposition occurred preferentially in neurones following
    silver lactate treatment. Electron-microscopical studies showed that
    silver was located intracellularly in the lysosomes and extracellularly in
    basement membranes and elastic fibres of the vessels.

Danscher G.  Stoltenberg M.  Juhl S. How to detect gold, silver and
mercury in human brain and other tissues by autometallographic silver
amplification. Neuropathology & Applied Neurobiology.  20(5):454-67, 1994
Oct.

ron      1936, dz PD 1984
Ronald F. Vetter <rfvetter@xxxxxxxxxxxxxxxx>