Another therapy for hexachlorophene's effects on the mitochondria of oligodendrocytes?

In the last entry I cited Lamictal's and topamax's therapeutic value. Here is how Seraquel/Quetiapine also might be able to address damages to oligodendrocytes by mitochondrial genetics or a mitochondrial neurotoxin. There are a number of research articles on cuprizone. The effectiveness of the mitochondrial cuprizone model in mice correlates with the hexachlorophene model in rats. Shouldn't both of their damages to oligodendrocytes be addressed by Seroquel/Quetiapine?

The second article addresses glucocorticoids and oligodendrocytes. This may also explain a reason that the cortisol-lowering Seroquel affects important changes to the oligodendrocytes.

Mol Psychiatry. 2007 Aug 7. [Epub ahead of print]

Related Articles,



Links

Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes.

Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, Li X, Dyck LE, Devon RM, Deng Y, Li XM.

1Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada.

Recent neuroimaging and postmortem studies have reported abnormalities in white matter of schizophrenic brains, suggesting the involvement of oligodendrocytes in the etiopathology of schizophrenia. This view is being supported by gene microarray studies showing the downregulation of genes related to oligodendrocyte function and myelination in schizophrenic brain compared to control subjects. However, there is currently little information available on the response of oligodendrocytes to antipsychotic drugs (APDs), which could be invaluable for corroborating the oligodendrocyte hypothesis. In this study we found: (1) quetiapine (QUE, an atypical APD) treatment in conjunction with addition of growth factors increased the proliferation of neural progenitors isolated from the cerebral cortex of embryonic rats; (2) QUE directed the differentiation of neural progenitors to oligodendrocyte lineage through extracellular signal-related kinases; (3) addition of QUE increased the synthesis of myelin basic protein and facilitated myelination in rat embryonic cortical aggregate cultures; (4) chronic administration of QUE to C57BL/6 mice prevented cortical demyelination and concomitant spatial working memory impairment induced by cuprizone, a neurotoxin. These findings suggest a new neural mechanism of antipsychotic action of QUE, and help to establish a role for oligodendrocytes in the etiopathology and treatment of schizophrenia.Molecular Psychiatry advance online publication, 7 August 2007; doi:10.1038/sj.mp.4002064.

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HERE IS THE CORTICOSTERONE -OLIGODENDROCYTE LINK THAT SEEMS TO GIVE ONE WAY FOR QUETIAPINE TO HAVE AN EFFECT THAT COUNTERS THE EARLIER HEXACHOROPHENE- OLIGODENDROCYTE TOXICITY.

GLIA 31:219-231, 2000.

Prolonged corticosterone treatment of adult rats inhibits the proliferation of oligodendrocyte progenitors present throughout white and gray matter regions of the brain

Gérard Alonso *
CNRS-UMR5101, CCIPE, Montpellier Cedex 05, France
email: Gérard Alonso (alonso@bacchus.montp.inserm.fr)
*Correspondence to Gérard Alonso, CNRS-UMR5101. CCIPE, 141 rue de la Cardonille, 34094 Montpellier Cedex 05, France
setDOI("ADOI=10.1002/1098-1136(200009)31:33.0.CO;2-R")
Keywords
glucocorticoids; astrocytes; microglia; germinative zones; remyelination
Abstract
It is well established that glucocorticoids inhibit the proliferation of progenitor cells that occurs in the hippocampal dentate gyrus of adult mammals. Active cell proliferation also occurs in the subventricular zone (SVZ) of the lateral ventricle and, to a lesser extent, throughout white and gray matter regions of the adult brain. The aim of the present study was to determine whether extrahippocampal cell proliferation is also affected by glucocorticoids. The cell proliferation marker bromodeoxyuridine (BrdU) was administered to control rats, to adrenalectomized rats, and to rats treated with a daily injection of corticosterone (10 mg/kg) for a period of 15 days. In control and adrenalectomized rats, high to low numerical densities of BrdU-labeled nuclei were detected within the different forebrain regions examined. In rats treated with corticosterone, a dramatic decrease of cell proliferation was detected in the dentate gyrus, but also throughout all white and gray matter regions examined, except for the SVZ of the lateral ventricle. Double-labeling experiments indicated that throughout the different white and gray forebrain regions examined, except for the SVZ, BrdU-labeled nuclei were essentially associated with cells immunostained for the marker of oligodendrocyte progenitors NG2. These data indicate that glucocorticoids inhibit the proliferation of oligodendrocyte precursors located throughout the white and gray matter regions of the adult rat brain. Since the proliferation of oligodendrocyte precursors plays a major role in the processes of remyelination, these data raise the question of possible detrimental effects of therapeutic treatments of CNS trauma based on the administration of glucocorticoids. GLIA 31:219-231, 2000. © 2000 Wiley-

Do these abstracts from PubMed indicate that there are potential uses of drugs to affect the current results of past hexachlorophene exposure?

Hexachlorophene caused damaging changes in oligodendrocytes that involved glutamate exciototoxicity.

These drugs adress oligodendrocytes abnormalities by blocking glutamate receptors. These and other ather articles indicate that drugs such as topiramate and lamictal would therefore be useful for oligdodedrocyte abnormalities.

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Trends Mol Med. 2006 Jul;12(7):289-92. Epub 2006 Jun 5.

Oligodendrocyte NMDA receptors: a novel therapeutic target.

Matute C.

Departamento de Neurociencias, Universidad del País Vasco, 48940-Leioa, Spain. carlos.matute@ehu.es

Excessive glutamate signaling can lead to excitotoxicity, a phenomenon whereby over-activation of glutamate receptors initiates neuronal death. In recent years, it has been shown that glutamate can be toxic to white-matter oligodendrocytes. Up to recently, the prevailing view was that oligodendrocyte excitotoxicity is mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate glutamate receptor types. Three recent studies have shown that oligodendrocytes also express N-methyl-D-aspartate (NMDA) receptors, which are activated under pathological conditions. Thus, NMDA receptors seem to be a promising target for the development of new drugs to treat white-matter damage in acute and chronic diseases.

Publication Types:

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Neurochem Res. 2008 Apr 26 [Epub ahead of print]Related Articles,

Metabotropic Glutamate Receptors in Glial Cells.

D'Antoni S, Berretta A, Bonaccorso CM, Bruno V, Aronica E, Nicoletti F, Catania MV.

Institute of Neurological Sciences, National Research Council, Vl Regina Margherita 6, 95123, Catania, Italy.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and exerts its actions via a number of ionotropic glutamate receptors/channels and metabotropic glutamate (mGlu) receptors. In addition to being expressed in neurons, glutamate receptors are expressed in different types of glial cells including astrocytes, oligodendrocytes, and microglia. Astrocytes are now recognized as dynamic signaling elements actively integrating neuronal inputs. Synaptic activity can evoke calcium signals in astrocytes, resulting in the release of gliotransmitters, such as glutamate, ATP, and D: -serine, which in turn modulate neuronal excitability and synaptic transmission. In addition, astrocytes, and microglia may play an important role in pathology such as brain trauma and neurodegeneration, limiting or amplifying the pathologic process leading to neuronal death. The present review will focus on recent advances on the role of mGlu receptors expressed in glial cells under physiologic and pathologic conditions.

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Glia. 2008 Jan 15;56(2):233-40.Related Articles, Links

Testing NMDA receptor block as a therapeutic strategy for reducing ischaemic damage to CNS white matter.

Bakiri Y, Hamilton NB, Káradóttir R, Attwell D.

Department of Physiology, University College London, London, England.

Damage to oligodendrocytes caused by glutamate release contributes to mental or physical handicap in periventricular leukomalacia, spinal cord injury, multiple sclerosis, and stroke, and has been attributed to activation of AMPA/kainate receptors. However, glutamate also activates unusual NMDA receptors in oligodendrocytes, which can generate an ion influx even at the resting potential in a physiological [Mg2+]. Here, we show that the clinically licensed NMDA receptor antagonist memantine blocks oligodendrocyte NMDA receptors at concentrations achieved therapeutically. Simulated ischaemia released glutamate which activated NMDA receptors, as well as AMPA/kainate receptors, on mature and precursor oligodendrocytes. Although blocking AMPA/kainate receptors alone during ischaemia had no effect, combining memantine with an AMPA/kainate receptor blocker, or applying the NMDA blocker MK-801 alone, improved recovery of the action potential in myelinated axons after the ischaemia. These data suggest NMDA receptor blockers as a potentially useful treatment for some white matter diseases and define conditions under which these blockers may be useful therapeutically. Our results highlight the importance of developing new antagonists selective for oligodendrocyte NMDA receptors based on their difference in subunit structure from most neuronal NMDA receptors. Copyright (c) 2007 Wiley-Liss, Inc.




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J Anat. 2007 Jun;210(6):693-702. Epub 2007 May 15.Related Articles,

Excitotoxic damage to white matter.

Matute C, Alberdi E, Domercq M, Sánchez-Gómez MV, Pérez-Samartín A, Rodríguez-Antigüedad A, Pérez-Cerdá F.

Departamento de Neurociencias, Universidad del País Vasco, Leioa, and Neurotek-UPV/EHU, Parque Tecnológico deBizkaia, Zamudio, Spain. carlos.,matute@ehu.es

Glutamate kills neurons by excitotoxicity, which is caused by sustained activation of glutamate receptors. In recent years, it has been shown that glutamate can also be toxic to white matter oligodendrocytes and to myelin by this mechanism. In particular, glutamate receptor-mediated injury to these cells can be triggered by activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate and N-methyl-D-aspartate glutamate receptor types. Thus, these receptor classes, and the intermediaries of the signal cascades they activate, are potential targets for drug development to treat white matter damage in acute and chronic diseases. In addition, alterations of glutamate homeostasis in white matter can determine glutamate injury to oligodendrocytes and myelin. Astrocytes are responsible for most glutamate uptake in synaptic and non-synaptic areas and consequently are the major regulators of glutamate homeostasis. Activated microglia in turn may secrete cytokines and generate radical oxygen species, which impair glutamate uptake and reduce the expression of glutamate transporters. Finally, oligodendrocytes also contribute to glutamate homeostasis. This review aims at summarizing the current knowledge about the mechanisms leading to oligodendrocyte cell death and demyelination as a consequence of alterations in glutamate signalling, and their clinical relevance to disease. In addition, we show evidence that oligodendrocytes can also be killed by ATP acting at P2X receptors. A thorough understanding of how oligodendrocytes and myelin are damaged by excitotoxicity will generate knowledge that can lead to improved therapeutic strategies to protect white matter.

Here is another way of assessing the presence of hexachlorophene in humans.

NeuroToxicology
Volume 28, Issue 2, March 2007, Pages 252-256
The 9th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health

Magnetic resonance for evaluation of toxic encephalopathies: Implications from animal experiments

Hideki Igisu^{a, ,} and Yoshimasa Kinoshita^b
aInstitute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
^bDepartment of Medical Informatics, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Received 19 October 2005; accepted 17 May 2006. Available online 22 May 2006.

Abstract

Examinations of brain of rats intoxicated with hexachlorophene or acrylamide with ultrahigh-field (4.7 T) proton magnetic resonance (MR) showed alterations consistent with clinical pictures in humans and morphological findings in experimental animals. On the other hand, conventional biochemical analyses have revealed that ethylene oxide, methyl bromide, and acrylamide inhibit creatine kinase (CK; an enzyme catalyzing the reaction: ATP + creatine ↔ ADP + phosphocreatine) activities in the brain of animals. Thus, ³¹P MR combined with magnetization transfer may be utilized to monitor living humans (or animals) intoxicated with these chemicals by determining CK activities in the target organ.

This article on diffusion tensor imaging is particularly relevant to perinatal mitochondrial neurotoxic injuries like hexachlorophene. Early detection, treatment and follow-up would make such a difference.

Diffusion tensor imaging of brain development
Petra S. Hüppi, a, and Jessica Duboisa
aDepartment of Pediatrics, Children's Hospital, University Hospitals of Geneva, 6, rue Willy-Donze, 1211 Geneva 14, Switzerland
Available online 8 September 2006.

Summary
Understanding early human brain development is of great clinical importance, as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral organization and maturation. Diffusion tensor imaging (DTI), a recent magnetic resonance (MR) modality which assesses water diffusion in biological tissues at a microstructural level, has revealed a powerful technique to explore the structural basis of normal brain development. In fact, the tissue organization can be probed non-invasively, and the age-related changes of diffusion parameters (mean diffusivity, anisotropy) reveal crucial maturational processes, such as white matter myelination. Nevertheless, the developing human brain presents several challenges for DTI applications compared with the adult brain. DTI may further be used to detect brain injury well before conventional MRI, as water diffusion changes are an early indicator of cellular injury. This is particularly critical in infants in the context of administration of neuroprotective therapies. Changes in diffusion characteristics further provide early evidence of both focal and diffuse white matter injury in association with periventricular leukomalacia in the preterm infant. Finally, with the development of 3D fiber tractography, the maturation of white matter connectivity can be followed throughout infant development into adulthood with the potential to study correlations between abnormalities on DTI and ultimate neurologic/cognitive outcome.

Introduction
Understanding early human brain development is of great clinical importance, as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral maturation. With conventional magnetic resonance imaging (MRI) we have been able to delineate macroscopically early developmental events such as myelination and gyral development. Diffusion tensor imaging (DTI) is a relatively new MR modality that assesses water diffusion in biological tissues at a microstructural level.1
The developing human brain presents several challenges for the application of DTI. Values for the water diffusion parameters differ markedly between pediatric brain and adult brain, and vary with age. As a result, much of the knowledge regarding DTI derived from studies of mature adult human brain is not directly applicable to developing brain. Yet in these challenges also lies opportunity, as changes in water mean diffusivity and diffusion anisotropy during development provide unique insight into the structural basis of brain maturation.
DTI may further be used to evaluate brain injury.2 It is well known from studies of animals3 and adult humans4 that DTI can serve as an early indicator of stroke, often demonstrating image abnormalities on water diffusion maps well before conventional MRI. Early detection of injury is particularly critical in the context of administration of neuroprotective therapies to infants. These therapies must be initiated quickly in order to interrupt the cascade of irreversible brain injury.5 Water diffusion maps derived from DTI may provide the means for this early detection of injury. Changes in diffusion characteristics further provide early evidence of both focal and diffuse brain injury in association with periventricular leukomalacia (PVL), the most common form of white matter injury in the preterm infant.6 Finally, with the development of 3D diffusion tensor fiber tractography, maturation of white matter and its consequences for white matter connectivity can be followed throughout infant development into adulthood, with the potential to study correlations between abnormalities on DTI and ultimate neurologic/cognitive outcome.7
In this review, we will discuss the changes in DTI parameters associated with normal brain maturation as well as their response to brain injury.

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DTI and functional development during childhood

Finally, DTI parameters – particularly anisotropy – may be considered as structural markers of the networks functional organization and maturation, as proposed recently by correlation studies in children and adolescents. For instance, the development of working memory and reading capacities, between 8 and 18 years of age, is linked to the white matter anisotropy in regions of the left frontal and temporal lobes.59 The maturation of these regions, as assessed by DTI, is correlated with the BOLD response amplitude, as measured by functional MRI.58 Reading capacities in normal and dyslexic children60 and 61 seem to depend on the organization and/or the myelination of temporo-parietal pathways, as described in adults.62 Finally, diffusion parameters appear to be immature in children with functional developmental delay.63 The application of DTI in the neonatal brain then provides an early assessment of its functional development, should it be normal or delayed.

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Conclusions

Important changes in water ADC and diffusion anisotropy accompany brain maturation. These changes reflect changes in brain tissue microstructure. In the case of grey matter, this may reflect changes in the dendritic architecture of pyramidal cells and the presence or absence of radial glial fibers. In the case of white matter, it is due to the establishment of white matter fiber connection and changes related both to ‘premyelination’ and myelination itself. Thus DTI is a unique, non-invasive technique to study brain maturation which can be readily applied to human development. DTI-based fiber tracking allows study of the establishment of brain connectivity and plasticity during a time period of extreme importance for structural and functional integrity of the brain.
DTI also allows detection of changes in response to brain injury. Decreases in the water ADC serve as an early indicator of brain injury relevant for initiation of neuroprotective treatments. Regional, maturation-dependent differences in baseline diffusion coefficients need to be considered when interpreting injury-related diffusion abnormalities. Chronic changes in water anisotropy and the evaluation by DTI vector imaging are sensitive to injury-related impairment of subsequent white matter development and brain connectivity, important early markers of later neurodevelopmental impairment. DTI in the newborn brain has allowed study of non-hemorrhagic brain injury early on, and has further opened up the possibility to study the structural correlate of functional impairment and plasticity in the developing brain.

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Here is another DTI article.

Autism and myelin/ white matter deficits:

Is there a relationship with the effects of mercury?

The link between autism and mercury is well beyond my ability to comment on, but his is an interesting study on the integrity of the white matter.

Again, this and other DTI research make me wonder about the value of Using this type of brain imaging to take another look at the toxicity of Hexachlorophene.

Would some of us exposed to this mitochondrial neurotoxin as babies also show white matter integrity problems on a DTI?

It certainly makes sense to look at those of us who are now young and older adults.

News-Medical.Net

New imaging technique reveals differences in brains of people with autism
Devices/Technology
Published: Monday, 23-Oct-2006


Using a new form of brain imaging known as diffusion tensor imaging (DTI), researchers in the Center for Cognitive Brain Imaging at Carnegie Mellon University have discovered that the so-called white matter in the brains of people with autism has lower structural integrity than in the brains of normal individuals.
This provides further evidence that the anatomical differences characterizing the brains of people with autism are related to the way those brains process information.
The results of this latest study were published in the journal NeuroReport. The scientists used DTI -- which tracks the movement of water through brain tissue -- to measure the structural integrity of the white matter that acts as cables to wire the parts of the brain together. Normally, water molecules move, or diffuse, in a direction parallel to the orientation of the nerve fibers of the white matter. They're aided by the coherent structure of the fibers and a process called myelination, in which a sheath is formed around the fibers that speeds nerve impulses. The movement of water is more dispersed if the structural integrity of the tissue is low -- i.e., if the fibers are less dense, less coherently organized, or less myelinated -- as it was with the participants with autism in the Carnegie Mellon study. Researchers found this dispersed pattern particularly in areas in and around the corpus callosum, the large band of nerve fibers that connects the two hemispheres of the brain.
"These reductions in white matter integrity may underlie the behavioral pattern observed in autism of narrowly-focused thought and weak coherence of different streams of thought," said Marcel Just, director of the Center for Cognitive Brain Imaging and a co-author of the latest study. "The new findings also provide supporting evidence for a new theory of autism that attributes the disorder to underconnectivity among brain regions," Just said.
In 2004, Just and his colleagues proposed the underconnectivity theory based on a groundbreaking study in which they discovered abnormalities in the white matter that suggested a lack of coordination among brain areas in people with autism. This theory helps explain a paradox of autism: Some people with autism have normal or even superior skills in some areas, while many other types of thinking are disordered.
Last summer, Just led a team of researchers that found for the first time that the abnormality in synchronization among brain areas is related to the abnormality in the white matter. They discovered that key portions of the corpus callosum seem to play a role in the limitation on synchronization. In people with autism, anatomical connectivity -- based on the size of the white matter -- was found to be positively correlated with functional connectivity, which is the synchronization of the active brain regions. They also found that the functional connectivity was lower in those participants in whom the autism was more severe.
These studies, along with the latest paper, are providing a comprehensive picture of the autistic brain, whose components operate with less coordination than is normally the case, and which is less reliant on frontal components and more reliant on posterior components. The latest DTI finding shows that some of the frontal-posterior communication fiber tracts are abnormal, consistent with the lower degree of frontal-posterior coordination.
"The brain components in autism function more like a jam session and less like a symphony," Just said.
http://www.cmu.edu/

A NEW HEXACHLOROPHENE BRAIN IMAGING ARTICLE

There is a new study of the effects of hexachlorophene shown on brain imaging. It's with animals ,but the author, Igisu, says this can lead to human imaging. Hopefully, this will eventually show long term hex effects on us savivors of hexachlorophene exposure..

Check last entry for my website, then links, then PubMed, then keyword hexachlorophene. Most Medical Libraries can let you get the full article on the internet.

I have been devoting some of my time lately to developing a website on Hexachlorophene Toxicity.

It's work in progress; it can be viewed at this address:

http://rremib.googlepages.com/home

I hope you find some of the information and the links useful.

An important focus of research on hexachlorophene and other mitochondrial neurotoxins is the search for drugs that block their lasting toxic effects. In both animal and human studies, drugs that affect a specific type of glutamate receptor affect the myelin in the brain.

In animal studies, these types of drugs block hexachophene's toxic effect. One of these drugs, NBQX, was effective in animals as a blocker of myelin damage. It is itself, however, toxic in humans.

With Brain Imaging of myelin the usefullness of similar drugs in humans could be assessed.

In those who were exposed to hexachlorophene as babies, drugs that would have blocked its toxic effects on the myelin then might also be of value now.

Here's an interesting new article on the value of Diffusion Tensor Imaging. I'm looking forward to it becoming more available in the future. Again, the article mentions specific advantages in studying the central nervous system white matter and myelin. For our community of past hexachlorophene babies and young children, DTI seems to me to be the key to getting specific research data on the long-term effects of hexachlorophene. It seems the DTI can measure specific bio-markers of specifically damaged myelin in selectively targeted brain locations indicative of hexachlorophene toxicity. Here is the article as reported by ABC Network:

New Brain Imaging Reveals Damage MRI Misses
Diffusion Tensor Imaging Shows Colorful Pictures
Feb. 17, 2006 — - When you look at the pictures of a brain from a typical MRI, it looks like an indistinguished blob. But the latest, cutting-edge technology called diffusion tensor imaging reveals the true wonders of the brain by developing the images into what looks like bundles of colorful wires -- thousands of them -- linking the brain's different parts. And to the patient, getting a DTI feels no different than getting an MRI.
The new imaging technology is only present in a few dozen research hospitals and not yet available to the average patient. But it already has far-reaching implications for those with head injuries because it can detect abnormalities that an MRI can't. Doctors will also be able to see more precisely how different drugs act on the brain and will be able to evaluate better the risks of brain surgery.
Of course, the brain itself is gray and white and not all of these fancy colors. If you go back to high school biology, you'll remember that the gray areas are where the processing takes place and the white matter is the connective channels that allow water to flow between various parts of the brain, making them work in coordination.
"If the white matter is normal, you're going to see it move in a direction," said Dr. Robert Zimmerman, a neuroimaging expert at Weill Medical College of Cornell University. "If the white matter is damaged, the water movement becomes chaotic."
If there is an interruption of this water movement, you're getting some impairment of brain function. By looking at where the bundles or connectors disappear, doctors can get some idea of what the effects of brain injury or disease will be.......

So, it seems to me, that this article and others show hexachlorophene's effects on myelin is really now able to be assesed "in vivo" by DTI. Comments?

BRAIN IMGING OF THE EFFECTS OF HEXACHLOROPHENE

I advocate the updating of hexachlorophene toxicity research by using the most appropriate advanced brain imaging technology. It is the purpose of this blog to raise questions about hexachlorophene on those babies who lived. This needs to be done with an open mind. We who were exposed to hexachlorophene , however, need to know more about its current effects on the white matter/ myelin of our central nervous system. My own library research is meant to raise necessary questions and suggest testable hypotheses. I do this in the hope that researchers whith more specific expertise become interested -- and active-- in reviving dormant hexachlophene research.

In light of that proposition, I invite comments by anyone on the usefullness and availability of a brain imaging technology for the effects of mitochondrial neurotoxins like hexachlorophene on myelin. It seems to me that diffusion tensor imaging (DTI) for white matter in specific brain regions ( e.g. cerebellum, hippocampus, etc.) is both diagnostic of hexachlorophene's current effects and of the potential use in testing the effectiveness of currently available therapeutic medications.

Again, I hope my research raises both interest and comments. Hexachlorophene has become the forgotten neurotoxin dispite its well researched lasting effects.

There are over 150 articles and advertisements about hexachlorophene in the New York Times. These are two of the articles that are worth looking up. I'm sorry I don't know how to get the full articles on to the blog.

============================================================================== F.D.A. CURBS USE OF GERMICIDE TIED TO INFANT DEATHS:Hexachlorophene Productsto Be Sold on Prescription and in Weaker Strengths GERMICIDE CURBS IMPOSED BYF.D.A.By RICHARD D. LYONSSpecial to The New York Times. New York Times (1857-Current file) New York, N.Y.:Sep 23, 1972. p. 1 (2 pp.)Author(s): By RICHARD D. LYONSSpecial to The New York TimesDocument types: front_pagePublication title: New York Times (1857-Current file). New York, N.Y.: Sep 23, 1972. pg. 1, 2 pgsSource type: Historical newspaperISSN/ISBN: 03624331ProQuest document 81961073ID:Text Word Count 871Document URL: http://proquest.umi.com/ pqdweb?did=81961073&Fmt=2&clientId=23438&RQT=309&VName=HNPAbstract (Document Summary)WASHINGTON, Sept. 22 -The Food and Drug Administration put under strict controltoday the germ killer hexachlorophene. The germicide, which is commonly used inthe home, has been linked to the deaths of 39 French babies this year.===============================================================================Document 2 of 2Brain Cell Energy Found Curbed by HexachloropheneBy JANE E. BRODY. New York Times (1857-Current file) New York, N.Y.:Mar 7,1972. p. 25 (1 pp.)Author(s): By JANE E. BRODYDocument types: articlePublication title: New York Times (1857-Current file). New York, N.Y.: Mar 7, 1972. pg. 25, 1 pgsSource type: Historical newspaperISSN/ISBN: 03624331ProQuest document 79426924ID:Text Word Count 481Document URL: http://proquest.umi.com/ pqdweb?did=79426924&Fmt=2&clientId=23438&RQT=309&VName=HNPAbstract (Document Summary)Two Bronx biochemists have found that the antibacterial chemicalhexachlorophene interferes with the ability of brain cells to produce theenergy they need to function properly.=============================================================================== Copyright © 2006 ProQuest Information and Learning Company. All rights reserved. Terms & Conditions [From ProQuest Company] Please do not reply directly to this email. Use the following link to contact ProQuest: http://www.proquest.com/division/cs-support.shtml

Medline Article Cita

Medline Article Citations

There are hundreds of articles about hexachlorophene cited in Pub Med.Since hexachlorophene (commonly known by one of its brand names, PhiSoHex) is effectively used to combat the bacteria staphylococcus, many of the citations concern this use.
However you can also see many of the hexachlorophene citations in the area of its toxicology. Particularly in the 60s and 70s, both human and animal research began to show the toxicological mechanisms of hexachlorophene. It should be noted that the accumulation of this research and the abnormalities of the autopsies of babies resulted in the severe restrictions on the use of hexachlorophene. Below are just a few of the numbers of relevant hexachlorophene citations.

National Library of Medicine Gateway listings:
In their search of Medline/Pub Med journal citations and abstracts they found 1207.
In their search of TOXLINE for toxicology citations they found 276.
In their search of DART for developmental and reproductive toxicology articles they found 65 citations.

Within Medline/PubMed one must be careful to note that the mere search for a word like hexachlorophene will turn up citations of articles where hexachlorophene is only a side issue. The same is especially true when hexachlorophene is one of two search words. Even so, it might be helpful to start an investigation of hexachlorophene’s toxicological effects by noting this: hexachlorophene with liver occurs in 70 articles; hexachlorophene with brain occurs in 113 articles; hexachlorophene and myelin occurs in 41 articles. I've noted in prior posts that some of the articles in each of these areas do indicate hexachlorophene toxicological effects in both animal and human studies.

neurochemical effect

This is another citation of hexachlorophene and other myelin toxins in a neurochemistry text.

Many chemical toxins can impair myelin formation or cause its breakdown
These include lead, cuprizone, lysolecithin, organotin, hexachlorophene and tellurium. Lead is a common environmental pollutant that causes hypomyelination and demyelination [1]. Cuprizone and lysolecithin are toxins that frequently have been used experimentally in the context of investigating remyelination [1, (image placeholder)5] (see below). Systemically administered cuprizone has a direct toxic effect on oligodendrocytes, whereas lysolecithin causes lysis of myelin sheaths themselves when administered focally. Triethyltin and hexachlorophene cause an edematous demyelination with splitting at the intraperiod line but without apparent damage to myelin-forming cells [1]. Tellurium treatment of young rats causes a highly synchronous demyelination and remyelination in sciatic nerve that is associated with the inhibition of cholesterol synthesis by some metabolite of this element [ (image placeholder)26]. A detailed description of the effects of these and other chemical toxins on the biochemistry of myelin is beyond the scope of this chapter, but they have been covered in more detail in earlier editions of this book or in other sources [1].
General undernourishment or dietary deficiencies of specific substances can lead to a preferential reduction in myelin formation
Much of the CNS myelin in mammals is formed during a relatively restricted time period of development, corresponding to the final prenatal months and the first few years of postnatal life in humans and 15 to 30 days of postnatal life in rats. Just before this rapid deposition of myelin, there is a burst of oligodendroglial proliferation. During these restricted periods of time, large portions of the metabolic activity and synthetic capacity of the brain are involved in myelinogenesis. Any metabolic insult during this "vulnerable" period may lead to a preferential reduction in myelin formation [1]. The most vulnerable period appears to be the time of oligodendroglia proliferation since animals deprived of food in this period have an irreversible deficit of myelin-forming cells and hypomyelination.

Hexachlorophene Toxi

Hexachlorophene Toxicity to French Babies

This is part of a Center For Disease Control report that briefly notes to French epidemiological study of the autopsies of the French babies who died after receiving hexachlorophene.



h. Hexachlorophene can be lethal from percutaneous absorption.  Children may be specifically susceptible. 
i. Hexachlorophene (6.3%) was added to “baby powder” in France due to a manufacturing error.  It caused encephalopathy and ulcerative skin lesions.  36 of 204 exposed children died within a few days of exposure (Martin-Bouyer et al., 1982). 
ii. pHisoHex® soap contains 3% hexachlorophene.  Repeated bathing of premature children in undiluted pHisoHex has been associated with a vacuolar encephalopathy and lower survival rates.  A study of 248 children autopsied over a 7.5 year period showed encephalopathy in 17 infants (Shuman et al., 1974).  PHisoHex has been restricted to prescription use or as a surgical scrub for health care personnel since 1972 (Freeman and Maibach, 1991).

At that time it was not possible to do brain imaging studies on the babies who lived.  Now of course it is possible.  It's certainly reasonable to expect that a pattern of abnormalities in the myelin may appear.  Based on hundreds of studies listed in Pub Med one might expect that two of the most likely structural areas of the brain may be the cerebellum and the brainstem.  

Mitochondria

Mitochondria
And
Neurological Disorders
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The Human Mitochondrial Neurotoxin, Hexachlorophene



The purpose of this paper is to raise some questions. They are based on a review of the biomedical research on mitochondria, neurological disorders, and the human neurotoxin, hexachlorophene. The questions, based upon the review, are raised in the hope that those with more specific expertise will see the value of exploring the quite real possibility that brain imaging of those who were exposed to hexachlorophene may show a specific pattern of neurological abnormalities. Will these brain imaging results of adults who were exposed to hexachlorophene as babies correlate with the specific pattern of neurological abnormalities shown in autopsies of the babies who died after being exposed to hexachlorophene?


Some questions raised are these: Today, who has those hexachlorophene-related mitochondrial abnormalities? We know babies and children are more vulnerable because the skin is more permeable, but what are the other exposure vulnerabilities. Are they, for some, also caused by an interaction with their specific genetics? Could brain imaging show abnormalities in the myelin of the cerebellum and other areas of the brain that are characteristic of this particular mitochondrial neurotoxin? Is there sufficient evidence to go ahead and assess a possible causal relationship between specific behavioral symptoms related to structural and functional brain abnormalities? Could brain imaging show a relationship between therapeutic variables, behavioral symptoms, and changes in structural and functional brain abnormalities?

Other mitochondrial neurotoxins (for example, triethyltins, cuprizone, MPTP,3-NP) have been used as causal variables in model neurological disorders (for example, Huntington's, ALS, Parkinson's, etc.). Each of these neurotoxins have different neurological effects. For example, a recent study(Klivenyi,P 2005) contrasted the effects of the toxin model for Parkinson's(MPTP) and the toxin model for Huntington's(3-NP). Both mitochondrial neurotoxins caused changes in amino acids. But they caused two different amino acid neurotransmitter effects. It would seem quite reasonable that a similar research approach would show that hexachlorophene would result in a third specific amino acid neurotransmitter effect. We know it has its own neurological disorder pattern.

From the past epidemiological study of the autopsies of the babies, we already know that it is a specific human mitochondrial neurotoxin. Hexachlorophene's effects, now, can be studied in adults by means of brain imaging. It's an opportunity that wasn't there before; it's an opportunity we should take advantage of now.

MITOCHONDRIAL NEUROT

MITOCHONDRIAL NEUROTOXINS AND OLIGODENDROCYTES/ MYELIN: THE HUMAN NEUROTOXIC PROCESS OF HEXACHLOROPHENE


Hexachlorophene is a mitochondrial neurotoxin that is especially toxic to developing oligodendrocytes. Myelin with water-filled spaces or vacuoles is a biomarker for hexachlorophene effects.

One of the ways in which hexachlorophene differs from other mitochondrial neurotoxins is the locations in the brain where it affects white and gray matter. Hexachlorophene is toxic to the cerebellum, the hippocampus and the brainstem among other areas of the brain.  One of the most consistent findings in both human and animal research with hexachlorophene is its toxicity to the cerebellum.

Research with humans in the late 60s and early 70s showed hexachlorophene’s neurotoxicity to babies.An epidemiological study in France found that babies who received talcum powder with hexachlorophene in excessive amounts, died.  Upon autopsy, they showed characteristic hexachlorophene abnormalities in their myelin.  About the same time, in America, research with babies and young children were showing examples of hexachlorophene related neurotoxicity.  As a result of this hexachlorophene use was severely restricted, essentially limited to adults.

One of those who participated in this research explained how difficult it was to do such research on such a widely used medical product.  It would seem that the difficulty must have continued.  One would expect more follow-up research on the possible long-term effects of hexachlorophene on those who received it at the vulnerable periods of their lives.

Two things have happened since that time.  One is that those who received hexachlorophene early in their lives are now in their 30s, 40s, 50s, and 60s.  Long-term effects on those who were most vulnerable are now possible.  The second thing has to do with brain imaging advancements.  The assessment of the long-term effects of hexachlorophene on both gray and white matter in the brain seems possible.

Effects of Mitochond

Effects of Mitochondrial Toxins Including Hexachlorophene : The Process of Liver Damage

Other papers have reviewed the effects of hexachlorophene as a mitochondrial neurotoxin. This paper will review an additional effect of hexachlorophene and other toxins of its preventing the mitochondrial production of ATP.
Adenosine Triphosphate (ATP) is vital because it is used to store energy in the cell's mitochondria. During oxidative stress this stored energy is used to defend the cell fom damage or death.

The specific result of these mitochondrial toxins on the liver is damage or death to the liver cells. In addition to hexachlorophene there are a number of herbicides and pesticides that affect the mitochondria of liver cells and, in turn, affect the viability of these cells. One of these herbicides is called dinoseb. Liver cell death by dinoseb starts in the mitochondria because it also leads to the depletion of ATP.

Another mitochondrial toxin to the liver is called Tacrine. It has been used in the treatment of Alzheimer's disease. However tacrine has been shown to accumulate within the mitochondria, and has targeted the mitochondrial DNA. Again, its effect of uncoupling oxidative phosphorylation is ATP depletion.

So,hexachlorophene, in addition to its neurological effects, is also toxic to liver cells. Again, hexachlorophene is a mitochondrial liver toxin as well as a neurotoxin. In both the brain and the liver it uncouples oxidative phosphorylation and interferes with the production of ATP. There is this same biochemical mechanism with similar effects. This depletion can result in either cellular damage or death. Repeated use of hexachlorophene repeats these toxic cellular effects.

This will be a blog about research dealing with the antibacterial, hexachlorophene. It will focus on hexachlorophene as a mitochondrial neurotoxin. It will cite both animal and human research that showed the toxic effects of hexachlorophene on the central nervous system myelin. It will focus on hexachlorophene's toxic effects on brain locations including the cerebellum, the hippocampus, and the brainstem.

Studies cited will include the epidemiological studies of the autopsies of babies in France who died after exposure to hexachlorophene and then showed its toxic effects in their myelin. There will also be citations of developmental effects of babies exposed to hexachlorophene. In addition to hundreds of studies about the mitochondrial neurotoxin, hexachlorophene, there have been an increasing number of recent studies of the effects of other mitochondrial neurotoxins on the central nervous system. Their effects, in many ways, reflect the common mitochondrial neurotoxic mechanism that they share with hexachlorophene.

It's especially interesting that these comparable mitochondrial neurotoxins and their effects are used as animal and human models of neurological and psychiatric disorders. These mitochondrial neurotoxins are used as models for Parkinson's, Huntington's, ALS, and other neurological disorders that affect different locations in the brain.

One of the most encouraging advancements in research is brain imaging of the effects of mitochondrial neurotoxins such as those that have become models of neurological and neuropsychiatric disorders.

In the early 1970s,when hexachlorophene was discovered to be a human mitochondrial neurotoxin, it only happened because autopsies were done after the deaths of those babies exposed to 6% hexachlorophene talcum powder. But now it is possible for hexachlorophene research to be updated. That is because its effects on those who lived can be investigated in the same way as other comparable neurotoxins have recently been reinvestigated.

Recent research on its fellow mitochondrial neurotoxins has resulted in much more information because brain imaging allows a much more sensitive exploration of the continuing toxic effects of these mitochondrial neurotoxins on the living brain. The question now is how much more we will find out when we use brain imaging to investigate what we already know is a comparatively toxic compound -- hexachlorophene.