IUBio

pathology of epilepsy

F. Frank LeFever flefever at ix.netcom.com
Thu Sep 24 22:34:12 EST 1998


Thanks.  And let me correct the posting you quoted (v. infra): I meant
to write "with medial rather than lateral fluid percussion" !

F. Frank



In <6u8hhq$ren$1 at fremont.ohsu.edu> Matt Jones <jonesmat at ohsu.edu>
writes: 
>
>In article <6u70ld$6uk at sjx-ixn9.ix.netcom.com> F. Frank LeFever,
>flefever at ix.netcom.com writes:
>>Thanks.  Will search out Soltesz (Magyar?).  Some people at Medical
>>College of Virginia have been working quietly away at stuff I
consider
>>very important.  With sagittal rather than medial fluid percussion
they
>>can get, depending on degree of impact, selective slight hippocampal
>>damage OR no histologically observable damage but with longterm
>>behavioral/cognitive effects.  I believe they have looked at GABA
>>changes, but much of their work has focused on cholinergic changes.
>>Lyeth and Hamm are two names that come to mind.
>>
>>re your Kapur and MacDonald reference: must be VERY recent; OVID disk
>>Medline search failed to locate it.
>>
>
>
>Here's the abstract for Kapur & Macdonald.
>J Neurosci 1997 Oct 1;17(19):7532-7540 
>
>Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity
of
>hippocampal dentate granule cell GABAA receptors.
>
>Kapur J, Macdonald RL
>
>Department of Neurology, University of Michigan Medical Center, Ann
>Arbor, Michigan 48104-1687, USA. 
>
>Fast synaptic inhibition in the forebrain is mediated primarily by
GABA
>acting on GABAA receptors (GABARs). GABARs are regulated by numerous
>positive (barbiturates, benzodiazepines, and neurosteroids) and
negative
>(picrotoxin, bicuculline, and Zn2+) allosteric modulators. The
>sensitivity of
>GABARs to GABA and to allosteric modulators changes gradually during
>normal development, during development of chronic epilepsy, and after
>prolonged exposure to GABAR agonists. Here we report the development
of
>rapid functional plasticity of GABARs occurring over 45 min of
continuous
>seizures (status epilepticus) in rats. Seizures induced in rats by
>administration of lithium followed by pilocarpine were readily
terminated
>by the
>benzodiazepine diazepam when administered early during the seizures
>(after 10 min of seizures). However, during status epilepticus, there
was
>a
>substantial reduction of diazepam potency for termination of the
>seizures. To determine whether the loss of sensitivity of the animals
to
>diazepam was
>caused by an alteration of GABAR functional properties, we obtained
>whole-cell GABAR currents from hippocampal dentate granule cells
isolated
>acutely from control rats and from rats undergoing status epilepticus.
>GABAR properties were characterized by determining GABA sensitivity
and
>the
>sensitivity of GABARs to regulation by benzodiazepines, barbiturates,
and
>Zn2+. When compared with those from naive controls, GABAR currents
>from rats undergoing status epilepticus were less sensitive to
diazepam
>and Zn2+ but retained their sensitivity to GABA and pentobarbital. We
>conclude
>that the prolonged seizures of status epilepticus rapidly altered the
>functional properties of hippocampal dentate granule cell GABARs. 
>
>PMID: 9295398, UI: 97442521 
>
>
>and here's the abstract for a Soltesz paper (yes, Magyar, the
Hungarian
>kind, not the Finnish kind).
>
>J Neurosci 1997 Nov 1;17(21):8106-8117 
>
>Instantaneous perturbation of dentate interneuronal networks by a
pressure
>wave-transient delivered to the neocortex.
>
>Toth Z, Hollrigel GS, Gorcs T, Soltesz I
>
>Department of Anatomy and Neurobiology, University of California,
Irvine,
>California 92697, USA. 
>
>Whole-cell patch-clamp recordings and immunocytochemical experiments
were
>performed to determine the short- and long-term effects of lateral
fluid
>percussion head injury on the perisomatic inhibitory control of
dentate
>granule cells in the adult rat, with special reference to the
development
>of
>trauma-induced hyperexcitability. One week after the delivery of a
>single, moderate (2.0-2.2 atm) mechanical pressure wave to the
neocortex,
>the
>feed-forward inhibitory control of dentate granule cell discharges was
>compromised, and the frequency of miniature IPSCs was decreased.
>Consistent
>with the electrophysiological data, the number of hilar parvalbumin
(PV)-
>and cholecystokinin (CCK)-positive dentate interneurons supplying the
>inhibitory innervation of the perisomatic region of granule cells was
>decreased weeks and months after head injury. The initial injury to
the
>hilar neurons
>took place instantaneously after the impact and did not require the
>recruitment of active physiological processes. Furthermore, the
decrease
>in the number
>of PV- and CCK-positive hilar interneurons was similar to the decrease
in
>the number of the AMPA-type glutamate receptor subunit
2/3-immunoreactive
>mossy cells, indicating that the pressure wave-transient causes
injurious
>physical stretching and bending of most cells that are large and not
>tightly
>packed in a cell layer. These results reveal for the first time that
>moderate pressure wave-transients, triggered by traumatic head injury
>episodes, impact
>the dentate neuronal network in a unique temporal and spatial pattern,
>resulting in a net decrease in the perisomatic control of granule cell
>discharges. 
>
>PMID: 9334386, UI: 97477430 
>
>
>Cheers,
>
>Matt




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