pathology of epilepsy

Matt Jones jonesmat at
Tue Sep 22 10:59:54 EST 1998

In article <6u70ld$6uk at> F. Frank LeFever,
flefever at 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
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
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
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
trauma-induced hyperexcitability. One week after the delivery of a
single, moderate (2.0-2.2 atm) mechanical pressure wave to the neocortex,
feed-forward inhibitory control of dentate granule cell discharges was
compromised, and the frequency of miniature IPSCs was decreased.
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
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

PMID: 9334386, UI: 97477430 



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