GLIA, MAMA MIA!

[Guest guest]

This is good stuff - maybe a multiple bell ringer..

http://www-med.stanford.edu/center/communications/Pressrel/September97/glial

..html

Lowly Glia Strengthen Brain Connections

STANFORD -- Once dismissed as mere padding, cells known as glia may be

essential for the correct wiring of the brain. This is the conclusion of

a study reported in the Sept. 12, 1997 issue of Science by researchers from

the Stanford University School of Medicine.

Postdoctoral fellow Pfrieger and Dr. Barbara Barres, associate

professor of neurobiology, used pure populations of nerve cells and glia

to show that, by themselves, the nerve cells connected together poorly,

but the combination of the two cell types resulted in strong connections

between nerve cells.

In the brain, such connections allow nerve cells to pass along messages

about our every sensation, thought and movement. Glia make up approximately

90 percent of the cells in the human brain, and yet researchers have

assigned mainly passive functions to them. Some glia wrap around nerve cells

and insulate them with a protein called MYELIN. Glia at synapses act both as

a physical barrier that prevents crossed wires and as a disposal unit that

mops up extra messenger molecules released by nerve cells.

The nerve cells chosen for the Stanford study -- retinal ganglion cells

-- lead from the eyes deep into the brain. Barres is using them as

representatives of a large class of nerve cells in the brain: those that

use a chemical messenger called glutamate to send a positive, or

excitatory, signal. The study did not address any effect of the glia on

the less prevalent nerve cells that send negative, or inhibitory,

signals.

It is also possible, she said, that glia control the strength of

synapses in the fully developed brain, beefing up some circuits and

turning down others. (and causing seizures when damaged? -lg)

http://weber.u.washington.edu/~chudler/glia.html

Glia: The Forgotten Brain Cell

The brain is made up of more than just nerve cells (neurons). While

there are about 100 billion neurons in the brain, there are about 10 to

50 times that many GLIAL CELLS in the brain. But do you hear much about

glia? NO! While glia cells do not carry nerve impulses (action

potentials) they do have many important functions...in fact, without

glia, the neurons would not work properly!

Types and Functions of Glia

Oligodendroglia - Provide the insulation (MYELIN) to neurons in the

central nervous system.

Schwann Cells - Provide the insulation (MYELIN) to neurons in the

peripheral nervous system.

Astrocyte (Astroglia) - Star-shaped cells that provide physical and

nutritional support for neurons:

1) clean up brain " debris " ;

2) transport nutrients to neurons;

3) hold neurons in place;

4) digest parts of dead neurons;

5) regulate content of extracellular space

Microglia - Like astrocytes, microglia digest parts of dead neurons.

Satellite Cells - Physical support to neurons in the peripheral nervous

system

http://spinwarp.ucsd.edu/NeuroWeb/Text/br-140.htm#anchor253716

To recognize abnormal myelination patterns, one must be aware of normal

myelination patterns:

Myelination Milestones

Brain stem, cerebellum, posterior limb of internal capsule: term birth.

Anterior limb internal capsule: two months.

Splenium of the corpus callosum: three months.

Genu corpus callosum: six months.

Occipital white matter - Central: five months (T1)/fourteen months (T2)

Peripheral: seven months (T1)/fifteen months (T2)

Frontal white matter - Central: six months (T1)/sixteen months (T2)

Peripheral: eleven months (T1)/eighteen months (T2)

http://www-med.stanford.edu/school/Neurosciences/faculty/msmith.html

The myelin sheath is necessary for normal function of most nerves of

vertebrate animals. Myelin formation is vulnerable to many metabolic

disorders due to genetic, nutritional, and/or environmental factors.

When myelin is deficient in its quantity or composition, the nerve

cannot function normally.

http://www.duke.edu/~pdrh/MLD.html

The Turnover of Myelin

Myelin is made up of a variety of insulating lipids in a mixture which

changes over time. The composition of myelin in an infant is quite different

from that of an adult (and infants' nerve impulses travel more slowly). The

supply of lipids for myelin, and the changes in myelin composition, are

provided by lipid processing enzymes. These are essential for the

maintenance of normal myelin on all the nerve axons.

http://www.trufax.org/vaccine/myelin.html

The Mechanism of Encephalitic Damage from Vaccines

The Myelin Sheath

An important part of human brain development involves the process of

myelination. A nerve is a conducting channel for electrochemical

impulses. The nerve can only conduct pulses of energy that a succession

of leaps along the fiber. Like insulation on an electric wire, the fatty

coating of myelin helps keep the pulses confined.

Brain Myelination Processes

At birth, relatively few pathways have myelin insulation, and the

myelination process in the human brain continues from before birth until

at least 20 years old. Up until the age of 10 or so, vast areas of the

cortex are not yet myelinated, and up to the age of 20, large areas of

the frontal lobes are not yet myelinated. [Ref: , The

Nervous System, (Philadelphia: J.B. Lippincott, 1969), p.296.;

Hart, Human Brain and Human Learning, (New York: Longman Inc., White

Plains) Books for Educators, Oak Creek, CA),p.119]

Myelination processes begin in the phylogenetically older parts of the

brain, such as the brain stem, and then moves to the areas of the

nervous system that have developed recently in humans, the prefrontal

lobe and cortex. The processes spread through the nervous system in

developmental stages which vary slightly in each individual.

The prefrontal portions of the cerebrum have a profound influence on

human behavior.[Hart, p.118] If an individual is injected with vaccines,

most of which have adjuvants which include mercury and aluminum

compounds and also include foreign proteins (many of them from other

species in which the vaccines are grown) and biological organisms,

unprotected nerves are impacted and alteration of neurological

development impacts subsequent behavior and learning patterns to one

degree or another.

In 1947, Isaac Karlin suggested that stuttering was caused by " delay in

the myelinization of the cortical areas in the brain concerned with

speech. " In 1988, research by Dietrich and others using MRI imaging of

the brains of infants and children from four days old to 36 months of

age have found that those who were developmentally delayed had immature

patterns of myelination.

It has also been found that impairment of these processes can alter

neural communication without necessarily causing severe CNS damage. So,

these facts have been satisfactorily proven by science, but ignored and

suppressed by mainstream medical establishment.

Vaccines, Neuroallergic Reaction and Brain Damage

The exact role of the allergic reaction in encephalitis was not

completely understood until about 1935, with the discovery by

Rivers of the phenomenon known as " experimental allergic

encephalomyelitis, " or (EAE). Up until 1935, it was assumed that

encephalitis was caused by some viral or bacterial infection of the

nervous system, and a search began in the 1920's for some organism that

might cause the problem. Rivers was able to produce brain

inflammation in laboratory monkeys by injecting them repeatedly with

extracts of sterile normal rabbit brain and spinal cord material, and

this made it quite apparent that encephalitis was an allergic reaction.

This explains the association of allergies and autoimmune states with

prior cases of encephalitis.

In 1922, the smallpox vaccination program caused an outbreak of

encephalitis, with a secondary result of Guillain-Barre Syndrome, an

ascending paralysis ending in death. For some reason, the fact that the

vaccinations were directly connected was hidden from the public until

1942. In 1953 it was realized that some of the epidemic children's

diseases, measles in particular, were demonstrating an increased

propensity to attack the central nervous system. This

indicated a growing allergic reaction in the population to both the

diseases and the vaccinations for the diseases. In 1978, British

researcher Bannister observed that the demyelinating diseases were

getting more serious " because of some abnormal process of sensitization

of the nervous system. "

I submit that the process of increased sensitivity was a normal

occurance - it could only be seen as abnormal if the connection between

the vaccines and the sensitization process, which by then should have

been obvious with the research conducted, was deliberately ignored. The

fact of the matter is that it is a matter of record that it was known

that vaccinations produced encephalitis since 1926. The sensitization of

the population was being enhanced by vaccination programs. Someone had

to know, since the connection was a matter of record.

We can see that the association between post-encephalitic syndrome and

either demyelination or incomplete myelination of the brain is pretty

straight forward. In might be mentioned at this point that polio, or

poliomyelitis, involves a breakdown of the myelin sheath, which causes

paralysis. We also know that encephalitis, whether caused through

disease or as a result of vaccination, can cause demyelination of the

nerves, and that this has been known since the 1920's.

http://www.lrz-muenchen.de/~u792201/www/microglia.html

Microglia, Cell of the Brain Decade

The biology and function of microglia is central to many issues in

modern neuropathology. Microglia and brain macrophages have been

recognized to play crucial roles in important diseases such as viral

infections, autoimmunity and neurodegenerative disorders. Encephalitis,

multiple sclerosis and Alzheimer's disease are

examples where understanding the role of microglia promises to hold

essential information concerning disease pathogenesis. In addition, it

is becoming increasingly clear that certain molecules expressed by

microglia have the potential of serving as diagnostic " sensors " in

day-to-day neuropathological practice. These markers point to subtle

tissue pathology that may otherwise go undetected (7-9).

June 1998:

http://www.sciencefriday.com/pages/features/0698/glial/glial.html

The way that neuroscientists look at most of our brain may be changing.

Glia, small cells that drastically outnumber their larger neighbors in

the brain, neurons, account for about half the brain's weight.

Traditionally, they have been characterized as mere support cells for

the brain's neural network, which sends electrical impulses along

complex routes to form the cellular basis for thought, learning and

memory. But now, scientists are finding that glial cells may play a much

greater role in the brain's communication than previously thought,

according to a recent report in the Journal of Neuroscience.

Newman and Kathleen Zahs, physiologists at the University of

Minnesota, have worked with rat retinas to show that when glia are

prodded, (or " stimulated mechanically " ), they can release calcium--which

can then influence communication between neurons. The calcium ions

emitted by one glial cell can trigger surrounding glia to release

calcium too, spreading a signal outwards like a the ripples caused by

throwing a stone into a pond.

" The calcium wave releases glutamate from the glial cells, " said Newman.

" We're not sure how it happens, but it has a direct impact on the firing

of the neurons. " Glutamate is a neurotransmitter, a chemical used by

neurons to communicate with each other.

Newman and Zahs showed that more than half of the neurons exposed to the

glutamate from glial cells changed either the speed or magnitude of

their firing.

http://www.hms.harvard.edu/dms/neuroscience/fac_corfas.html

Neuron-glia interactions play critical roles in several steps of nervous

system development, including neuronal migration, neuronal

differentiation, and synapse formation and function.

http://spinwarp.ucsd.edu/NeuroWeb/Text/br-140.htm#anchor253716

Metabolic Destructive Lesions

Abnormalities usually due to enzyme deficiencies leading to errors of

aerobic metabolism (defects in the Krebbs cycle) lead to global

abnormalities which are usually manifested by symmetrical defects in

areas that have high oxygen and other metabolic requirements. These

include the basalganglia and the thalami as well as parts of the

brain stem.

The melas (mydrocondrial encephalopathy, lactic acidosis, stroke)

syndrome also may be seen with defects in the basalganglia as well as

multiple cortical infarctions in a nonvascular distribution

predominantly in the occipital lobes. Other metabolic misfires such as

maple syrup urine disease may be seen diffuse cerebral edema.

Therefore bilaterally symmetrical abnormalities (especially if centered

at the basalganglia) should make one think very strongly of an

underlying metabolic process.

http://www3.cac.washington.edu/medical/som/industry_relations/schwartzkroin.

html

Changes in extracellular space (ECS) have been studied within the

context of a variety of neuropathologies, including head trauma. ECS has

been somewhat neglected within the epilepsy field, even though there are

several studies that suggest contributions of ephaptic interactions

(current flow through extracellular space) to increased excitability,

hyper-synchrony and seizure spread. Further, experiments have shown that

changes in extracellular fluid osmolality can modify

brain seizure threshold.

http://www.zmbh.uni-heidelberg.de/Nave/Report.html

Myelin-forming glial cells provide a model system to study principles of

neuron-glia interactions and cellular differentiation in the mammalian

nervous system. The assembly of myelin sheaths is the highly specialized

function of oligodendrocytes in the CNS and Schwann cells in the periphery.

Myelin-forming glial cells enwrap axons with multiple layers of membrane

and provide the electrical insulation that is necessary for a rapid

impulse propagation.

http://206.63.58.44/trauma.htm

The process by which brain contusions produce brain necrosis is

complex and is also prolonged over a period of hours. Toxic processes

include the release of free oxygenradicals, damage to cell membranes,

opening of ion channels to influx of calcium, release of cytokines and

metabolism of free fatty acids into highly reactive substances that may

cause vascular spasm and ischaemia. Such processes may also be

interruptable by therapeutic agents such as lipid antioxidants, calcium

channel blockers, and glutamate antagonists. The search for secure evidence

that new classes of drug based on these mechanisms reduce the morbidity and

mortality of brain injury will be one of the most important efforts of the

nineties.

Free radicals are formed at some point in almost every mechanism of

secondary injury. Their primary targets are the fatty acids of the

cell-membrane. A process known as lipid peroxidation damages neuronal, glial

and vascular cell membranes in a geometrically progressing fashion. If

unchecked, lipid peroxidation spreads over the surface of the cell membrane

and eventually leads to cell death. Thus free radicals damage endothelial

cells, disrupt the blood-brain barrier, and directly injure brain cells,

causing edema and structural changes in neuronsand glia. Disruption of

the blood-brain barrier is responsible for brain edema and exposure of brain

cells to damaging blood-borne products.

http://molebio.iastate.edu/~p_haydon/astro.pub

Calcium-dependent glutamate release from astrocytes

In the CNS glia out-number neurons 10 to 1. Despite their numerical

superiority the roles of glial cells are not fully understood.

Initially, Rudolf Verchow (1895) described glia (Greek for glue) as the

real cement that holds the nervous elements together. It is now clear

that glia play many roles. Glia can be divided into three sub-categories,

astrocytes, oligodendrocytes and microglia. Our work has focussed on the

roles of astrocytes play in the CNS. In 1994 four independent groups

have demonstrated that astrocytes can signal directly to neurons. We

have shown that astrocytes and Schwann cells can release the excitatory

amino acids glutamate and aspartate in response to elevated internal

calcium levels (1-3). Furthermore, when neurons are co-cultured with

astrocytes calcium-dependent release of glutamate from astrocytes leads

to a NMDA receptor dependent elevation of neuronal calcium (1). What

might be the role of such a signaling pathway. Perhaps astrocytes play a

neuromodulatory role by clamping the external level of excitatory amino

acids through a combination of regulated transmitter uptake and

release.

Astrocytes Modulate Synaptic Transmission

To study the regulation of synaptic transmission we stimulated

astrocytes locally either with mechanical or with electrical stimuli

that can promote calcium waves. Then, recording from neurons with patch

pipettes we monitored the consequences on neuronal properties. We have

shown that a calcium elevation in astrocytes is both necessary and

sufficient to modulate synaptic transmission and to activate ionotropic

glutamate receptors on hippocampal neurons(4-5). These data suggest that

astrocytes can dynamically regulate the neuronal excitability and

synaptic transmission.

Relevent publications

1) Parpura, V., Basarsky, T.B., Liu, F., Jeftinija, S., Jeftinjia, S.,

and Haydon, P.G. (1994) Glutamate- mediated astrocyte-neuron signaling.

Nature 369: 744-747. abstract

2) Parpura, V., Liu,F., Brethorst, S., Jeftinija, K., Jeftinija, S., and

Haydon, P.G. (1995) a-latrotoxin stimulates glutamate release cortical

astrocytes in cell culture. FEBS Letts. 360: 266-270. abstract

3) Parpura, V., Liu, F., Jeftinija,K., Jeftinija,S., and Haydon, P.G.

Neuroligand-evoked calcium- dependent release of excitatory amino acids

from Schwann cells.The Journal of Neuroscience. 1995 August; 15(8):

5831-5839

.. abstract

4) Araque, A, Parpura, V., Sanzgiri, R.P. and Haydon, P.G. (1998)

Astrocytes modulate hippocampal synaptic transmission. European Journal

of Neuroscience. 10: 2129-2142.

5) Araque, A., Sanzgiri, R.P., Parpura, V., and Haydon, P.G. (1998)

Calcium elevation in astrocytes causes an NMDA receptor-dependent

increase in the frequency of miniature synaptic currents in cultured

hippocampal neurons. J. Neuroscience. 18: 6822-6829. [full text (PDF)]