Quantitative analysis of parvalbumin-immunoreactive cells in the human epileptic hippocampus

doi:10.1016/j.neuroscience.2007.07.029

Neuroscience

Volume 149, Issue 1, 12 October 2007, Pages 131-143

https://doi.org/10.1016/j.neuroscience.2007.07.029 Get rights and content

Abstract

Hippocampal sclerosis is the most frequent pathology encountered in mesial temporal structures resected from patients with intractable temporal lobe epilepsy and it mainly involves hippocampal neuronal loss and gliosis. These alterations are accompanied by changes in the expression of a variety of molecules in the surviving neurons, as well as axonal reorganization in both excitatory and inhibitory circuits. The alteration of a subpopulation of GABAergic interneurons that expresses the calcium binding protein parvalbumin (PV) is thought to be a key factor in the epileptogenic process. We investigated the distribution and density of parvalbumin-immunoreactive (PV-ir) neurons in surgically resected hippocampal tissue from epileptic patients with and without sclerosis. Using quantitative stereological methods, we show for the first time that there is no correlation between total neuronal loss and PV-ir neuronal loss in any of the hippocampal fields. We also observed higher values of the total neuronal density in the sclerotic subiculum, which is accompanied by a lower density of PV-ir when compared with non-sclerotic epileptic and autopsy hippocampi. These findings suggest that, the apparently normal subiculum from sclerotic patients also shows unexpected changes in the density and proportion of PV-ir neurons.

Section snippets

Experimental procedures

Human brain tissue was obtained from two sources: from autopsies (supplied by Dr. R. Alcaraz, Forensic Pathology Service, Basque Institute of Legal Medicine, Bilbao, Spain) and postoperative tissue from 11 patients, suffering pharmacoresistant TLE (Department of Neurosurgery, Hospital de la Princesa, Madrid, Spain).

According to the Helsinki Declaration, the patient’s consent was obtained in all cases (BMJ 1991;302:1194) and all protocols were approved by the institutional ethical committee

Results

The cytoarchitectonic division of the hippocampal fields (Fig. 1A) was established on basis of the descriptions in Amaral and Insausti (1990), but also considering the CA4 field according to the definition of Rosene and Van Hoesen (1987).

The distinction between CA1 and the subiculum was established by the presence of clusters of modified pyramidal cells in the superficial aspect of the subiculum (Fig. 1). The CA1 field was divided in three subfields to account for the regional differences in

Discussion

In the current study, we have used quantitative methods to show for the first time that the lower density of PV-ir cells is not directly related to the overall loss of neurons in the human sclerotic hippocampus. Indeed, this is the case both in the polymorphic layer of the DG and in the stratum pyramidale of the CA fields. We also observed a notable greater overall neuron density coupled with a severe decrease in the density of PV-ir cells in the subiculum of sclerotic hippocampi when compared

Acknowledgments

We thank Dr. R. G. Sola and his team (Neurosurgery Service, Hospital de la Princesa, Madrid, Spain) for providing the tissue from epileptic patients and for their contributions, and we thank R. F. Senso for technical assistance.

This work was supported by the following institutions: Spanish Ministry of Education and Science (BFI2003-02745, BFI2003-01018, BFU2006-13395); Comunidad de Madrid (grant 08.5/0027/2001.1); and research fellowships for A.A. (Ricerca Fondazione Mariani, Grant R-04-40) and

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¹: Both authors contributed equally to this work.

²: Present address: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

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Developmental neuroscienceQuantitative analysis of parvalbumin-immunoreactive cells in the human epileptic hippocampus

Abstract

Section snippets

Experimental procedures

Results

Discussion

Acknowledgments

Neurobiol Dis

Neuroscience

Epilepsy Behav

Brain Res

Brain Res

Brain Dev

Trends Neurosci

Brain Res

Epilepsy Res

Neuroscience

Neuron

Epilepsy Res

Brain Res

Epilepsy Res

Prog Neurobiol

Neuroscience

Neuroscience

Microanatomy of the dysplastic neocortex from epileptic patients

Brain

Calcium-binding proteins: selective markers of nerve cells

Cell Tissue Res

Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus

Brain

Is epilepsy a disorder of inhibition or excitation?

Prog Clin Biol Res

Temporal lobe volumetric cell densities in temporal lobe epilepsy

Epilepsia

Neuronal, dendritic, and vascular profiles of human temporal lobe epilepsy correlated with cellular physiology in vivo

Adv Neurol

Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus

J Neurosci

Brain plasticity and cellular mechanisms of epileptogenesis in human and experimental cortical dysplasia

Epilepsia

Cellular pathology of hilar neurons in Ammon’s horn sclerosis

J Comp Neurol

Parvalbumin-immunoreactive structures in the hippocampus of the human adult

Cell Tissue Res

On the structure of the human archicortexI. The cornu ammonis A Golgi and pigment architectonic study

Cell Tissue Res

Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity

Proc Natl Acad Sci U S A

The anatomical connections of the macaque monkey orbitofrontal cortexA review

Cereb Cortex

Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex

Science

On the origin of interictal activity in human temporal lobe epilepsy in vitro

Science

Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons

J Neurosci

Quantitative neuropathology of the entorhinal cortex region in patients with hippocampal sclerosis and temporal lobe epilepsy

Epilepsia

Developmental neuroscience
Quantitative analysis of parvalbumin-immunoreactive cells in the human epileptic hippocampus

Axonal action-potential initiation and Na⁺ channel densities in the soma and axon initial segment of subicular pyramidal neurons