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Journal of Neuroscience, Vol 9, 2562-2574, Copyright © 1989 by Society for Neuroscience
Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus
TL Babb, JK Pretorius, WR Kupfer and PH Crandall
Department of Neurology, UCLA School of Medicine, University of California 90024.
The present study was designed to determine whether inhibitory neurons in
human epileptic hippocampus are reduced in number, which could reduce
inhibition on principal cells and thereby be a basis for seizure
susceptibility. We studied the distribution of GABA neurons and puncta by
using glutamate decarboxylase (GAD) immunocytochemistry (ICC) together with
Nissl stains. Using quantitative comparisons of GAD- immunoreactive
(GAD-IR) neurons and puncta in human epileptic hippocampus and in the
normal monkey hippocampus, we found that GAD-IR neurons and puncta are
relatively unaffected by the hippocampal sclerosis typical of hippocampal
epilepsy where 50-90% of principal (non-GAD-IR) cells are lost. GAD-IR
neurons and puncta were not significantly decreased compared with normal
monkey. In 6 patients, prior in vivo electrophysiology demonstrated that
the anterior hippocampus generated all seizures. The anterior and posterior
hippocampus were processed simultaneously, and the counts of hippocampal
GAD-IR neurons were numerically greater in anterior than in the posterior
hippocampus, where no seizures were initiated. These results indicate that
GABA neurons are intact in sclerotic and epileptogenic hippocampus.
Computerized image analysis of puncta densities in fascia dentata, Ammon's
horn, and subicular complex in epileptic hippocampi (n = 7) were not
different from puncta densities in the same regions in normal monkey (n =
2). Hence, despite the significant loss of principal cells (50-90% loss)
GABA terminals (GAD- IR puncta) were normal, which suggests GABA
hyperinnervation of the remnant pyramidal cells and/or dendrites in human
epileptic hippocampus. The apparent increase in puncta ranged from 2
(fascia dentata) to 3.3 (CA1) times normal puncta densities. These findings
would suggest increased inhibition and less excitability; however, those
regions were epileptogenic. We suggest that GABA terminal sprouting or
hyperinnervation of the few remnant projection cells may serve to
synchronize their membrane potentials so that subsequent excitatory inputs
will trigger a larger population of neurons for seizure onset in the
hippocampus and propagation out to undamaged regions of subiculum and
neocortex.
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