Abstract
Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.
Highlights
Temporal lobe epilepsy (TLE) is a common form of intractable epilepsy in which the most frequent pathology encountered in resected mesial temporal tissue is hippocampal sclerosis (Honavar et al, 1997)
Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity
Using correlative light and electron microscopy, we have shown here that the number of synapses per volume is selectively altered in specific regions of the sclerotic hippocampus when compared to the non-sclerotic hippocampus of epileptic patients
Summary
Temporal lobe epilepsy (TLE) is a common form of intractable epilepsy in which the most frequent pathology encountered in resected mesial temporal tissue is hippocampal sclerosis (Honavar et al, 1997). Hippocampal sclerosis is characterized by gliosis and neuronal loss, most prominently in the CA1 field, followed by the CA3 and CA2 fields, and the dentate gyrus (Houser, 1992; Honavar et al, 1997) This neuronal loss and gliosis is accompanied by changes in the expression of a variety of molecules in the surviving cells, as well as by axonal reorganization involving both excitatory and inhibitory circuits (e.g., de Lanerolle et al, 1989; Sutula et al, 1989; Babb et al, 1991, 2000; Sloviter, 1991; Muñoz et al, 2002, 2007; Wittner et al, 2002; Arellano et al, 2004).
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