DC lesion?

k p Collins kpaulc at [----------]earthlink.net
Sat Feb 14 23:47:27 EST 2004


"NMF" <nm_fournier at ns.sympatico.ca> wrote in message
news:f7AXb.13327$lK.895683 at news20.bellglobal.com...
> Thanks for the reference.  I am familiar with Post's work and I have seen
> papers on the quenching procedure that employed low frequency stimulation
as
> a means to depotentiate epileptogenic foci before, however.  I haven't
read
> any of his low intensity current work.  The low frequency paradigm they
> adopted is routinely employed to study long-term depression in the
> hippocampus, neocortex, cerebellum, etc.  I think 15 microAmp stimulation
> had the most advantageous effect for retarding the development of
kindling.
> In the reference you provided, the authors suggested that the quenching
> effects did not depend upon low frequency stimulation especially since
> low-frequency stimulation did not appear to change or diminish the
> ameliorative effects of DC stimulation. (This is an extremely important
> point because this suggestion contradicts their own previous work and the
> work of others on this matter).
>
> I thought it was interesting to note that they have reported a dense
silver
> staining surrounding the foci region.  The silver staining at least
suggests
> the possibility of degrading neurons within the region, but it is quite
> unfortunate that they did not assess necrosis or apoptosis in their
animals.
> What I thought was interesting was that there unpublished studies showed
> increased GFAP (a glial cell marker) within this silver staining "halo".
> Considering that the most likely labeled cells would be astrocytes and
> considering the homeostatic and regulatory role that these cells play
> especially during epilepsy, it seems very likely that these could be the
> targets that may be actively responsible for modulating the responsiveness
> of these "epileptic" neurons during their kindling procedure.
>
>  I don't buy the gap junction possibility that was suggested earlier
simply
> because gap junctions are not that ubiquitous within the basolateral
> amygala.  Perhaps if the AD threshold changes were recorded in the dentate
> or CA1, then perhaps gap junctions would be at least partially
responsible.
> Moreover, it has been well-established that continual low frequency
> stimulation can cause significant changes to the GABA receptor, such that
> increased binding can occur at the benzodiazepine binding site in the
> GABA(A) receptor.  Perhaps receptor changes similar to this can occur
during
> the DC stimulation.
>
> I am quite surprise that they never considered that these low threshold
> currents may in fact activate different calcium channels during
stimulation.
> They basically ignored the possibility that gene transcription and
> subsequent protein synthesis may be one of the causal factors involved in
> mediating this effect, especially in light of the long-lasting effect that
> this DC stimulation paradigm had.  Specific frequencies of stimulation and
> even different intensities of current have all been shown to activate,
> modulate, and suppress voltage-dependent calcium channels differently.
> Moreover, spatiotemporal modulation of these channels would evoke
different
> signal cascades within the cell that could lead to transient enhancement
or
> transient suppression in excitatory properties of neurons (see Johnston
and
> Magee).
>
> As far as clinical efficacy goes it seems really interesting and
promising.
> I did a very quick first-order calculation of habituation that would occur
> from these cells in response to the 15 min. DC current stimulations daily.
> Habituation to this stimulation protocol would occur around 96 days. That
is
> theoretically the neurons should stop responding to the DC current by this
> time point. If the scaring can be prevented this might serve as an
extremely
> useful adjunctive treatment.
>
> NMF

Do you realize that, except for what I'll discuss below,
you've just reiterated my previous discussion without
integrating what you've reiterated?

Although, if it continues indefinitely, it'll probably
have physiologically-deleterious effects, there's
nothing intrinsic in low-level DC that can be "hab-
ituated" to. It 'just', local to its injection, shifts
membrane potential, and everything else that
occurs operates upon that shifted membrane
potential, 'seeing' it as being 'normal' [which is
what results in the "tuning-precision void" after
the DC is withdrawn. And why there should
also be subtle "supersystem configuration"
'abnormalities' post-DC-injection [see AoK, Ap5].

K. P. Collins

> "Klenow" <bakedbeans at spam.not> wrote in message
> news:afkXb.32855$9U3.29342 at fe09.usenetserver.com...
> > In our journal club, we were discussing their chapter in the book
Kindling
> 5
> > where they describe the Quenching effect on kindling.  We're pretty
> > skeptical about it so we looked to see what else they had done on it.
I'm
> > curious to know what people think of this.
> >
> > Here's the article...
> >
> > 1: Exp Neurol.  1998 Nov;154(1):185-92.
> >
> > Quenching revisited: low level direct current inhibits amygdala-kindled
> > seizures.
> >
> > Weiss SR, Eidsath A, Li XL, Heynen T, Post RM.
> >
> > Biological Psychiatry Branch, National Institute of Mental Health,
> Bethesda,
> > Maryland 20892, USA.
> >
> > We have reported that low frequency stimulation (1 Hz for 15 min),
applied
> > after
> > kindling stimulation of the amygdala, inhibited the development and
> > expression
> > of amygdala-kindled seizures, an effect we termed quenching.
Subsequently,
> > we
> > discovered that this effect could only be achieved when certain
> stimulators
> > were
> > used that also emitted a low-level direct current (DC). The studies
> reported
> > here indicate that DC, applied once daily for 15 min at intensities of
> 5-15
> > microA, produced an intensity-related attenuation of kindling
development
> > and an
> > increase in the afterdischarge threshold. This effect persisted in some
> > animals
> > for at least 1 month after discontinuation of the DC. In fully kindled
> > animals,
> > a robust increase in seizure threshold and persistent seizure inhibition
> > were
> > also observed using 10 microA of DC administered for 14 days. These
> results
> > clarify and extend our original findings of a quenching effect; however,
> the
> > mechanisms by which low level DC induces quenching require further
> > elucidation.
> >
> >
> > "NMF" <nm_fournier at ns.sympatico.ca> wrote in message
> > news:JEjXb.17152$sO4.1541938 at news20.bellglobal.com...
> > > Your right that really is a low current, however, depending on where
> they
> > > implanted the electrode you might be able produce an electrolytic
lesion
> > > with extremely low current.  It might depend on whether they were
using
> > > monophasic, biphasic fast ramps to deliever the stimulus current.
> > However,
> > > I think you said it was a low but constant current intensity, so
square
> > wave
> > > currents (which can elicit lesions at very low current intensities)
are
> > out
> > > of the picture.   For example, in the dentate with a low intensity
> current
> > > many cells have been shown to readily elicit prolonged burst firing.
> The
> > > prolonged period of burst firing will allow for greater calcium
entrance
> > > into the cell and the potential for deleterious accumulations of
> > > intracellular calcium, activation of internal stores, and
consequential
> > > secondary messenger cascades.
> > >
> > > Generally the microcurrents used in many peripheral nerve stimulation
> > > experiments are in the 50-100 microAmp range.  Moreover, they elicit
> > potent
> > > analgesic responses.  (This is the premise of electroacupuncture
> > paradigms).
> > > So definitely potent cellular responses are likely at the low currents
> you
> > > suggest.  As an aside point, even picotesla intensity magnetic fields
> have
> > > been shown to elicit profound neuronal responses. (no evidence of
cystic
> > > lesions though).  So definitely low intensity currents can elicit
potent
> > > biological effects.
> > >
> > > Technically, it doesn't surprise me all that much that you can get a
> > > deleterious effect with such low intensity.  The cellular responses to
> > > electrical stimulation is often a U-shaped curve. With extremely
minimal
> > > currents eliciting similar effects to that of high intensity currents.
> In
> > > this case its probably the temporal component (the fact that its a
long
> > > duration low intensity current) that is causing the effect similar to
> what
> > > would be encountered at higher intensity currents but have short time
> > range.
> > > That is also a common finding in sensory and motoric systems.  But its
> > also
> > > a routine finding in the literature involving learning and LTP vs. LTD
> > > (long-term potentation vs. long-term depression), where the specific
> level
> > > of current intensity determines which type of behavioral
(physiological)
> > > response occurs.
> > >
> > > I wouldn't mind if you provided the citation to that paper.
> > >
> > > Thanks,
> > >
> > > NMF
> > >
> > >
> > >
> > > "Klenow" <bakedbeans at spam.not> wrote in message
> > > news:PxiXb.9020$%h1.7659 at fe24.usenetserver.com...
> > > >
> > > > I've recently read a paper looking at the effects of 15 minutes of
> > direct
> > > > current stimulation (5-15 uA) through a chronic indwelling electrode
> on
> > > > kindled seizure thresholds in rats.  Can this type of stimulation
> cause
> > an
> > > > electrolytic lesion at the electrode tip even with such low current?
> > I've
> > > > been looking through brain stimulation books and can't find an
answer.
> > > >
> > > > --
> > > > -----
> > > >
> > > >
> > > >
> > >
> > >
> >
> >
> >
>
>





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