REACTIVE SYNAPTOGENESIS AND NEURON DENSITIES FOR NEUROPEPTIDE-Y, SOMATOSTATIN, AND GLUTAMATE-DECARBOXYLASE IMMUNOREACTIVITY IN THE EPILEPTOGENIC HUMAN FASCIA-DENTATA

This study determined differences of fascia dentata (FD) peptide and i nhibitory neuroanatomy between patients with epileptogenic hippocampal sclerosis (HS), those with extrahippocampal seizure pathologies, and autopsy comparisons. Surgically treated temporal robe epilepsy patient s were clinically classified into two pathogenic categories: (1) HS wi th focal mesial temporal neuroimaging and histories of initial precipi tating injuries to the brain (n = 18) and (2) non-HS patients with ext rahippocampal mass lesions or idiopathic seizures (i.e., without lesio ns or HS; mass lesion/idiopathic; n = 9). The hippocampal sections wer e studied for (1) granule cell, hilar, CA4, and CA3 neuron densities; (2) hilar densities and the percentage of neurons immunoreactive (IR) for neuropeptide Y (NPY), somatostatin (SS), and glutamate decarboxyla se (GAD); (3) densities of GAD neurons in the lower granule cell and i nfragranular zone (basket-like cells); (4) the semiquantitative patter n of IR peptides/GAD FD molecular layer axon sprouting; (5) IR gray va lues (GV) of the FD molecular layers; and (6) the thickness of the sup ragranular molecular layer. Results showed the following. (1) Compared to autopsies, both HS and mass lesion/idiopathic patients showed less granule cell and CA3 neuron densities, but there were no statistical differences between the latter two pathogenic categories. (2) By contr ast, compared to autopsies and mass lesion/idiopathic cases, HS patien ts showed less hilar and CA4 neuron densities, and there were no diffe rences between autopsies and mass lesion/idiopathic. (3) Compared to a utopsies, the NPY and SS hilar neuron densities in HS patients, but no t mass lesion/idiopathic cases, were less. (4) Compared to autopsies, the hilar GAD neuron densities for HS and mass lesion/idiopathic patie nts were not less. (5) In HS patients the averaged percentages of hila r SS neurons were less than autopsies, and no other differences of IR hilar percentages were found. (6) The densities of GAD basket-like neu rons and the thickness of the supragranular molecular layer were not d ifferent between any combination of pathogenic categories and autopsie s. (7) By semiquantitative visual assessments, peptides/GAD axon sprou ting into the FD was greater in HS compared to mass lesion/idiopathic or autopsies. (8) Compared to mass lesion/idiopathic cases, in HS NPY outer molecular layer GVs were lower, SS GVs were not different, and G AD inner molecular layer GVs were higher. (9) Analyses comparing the t wo pathogenic categories and neuron densities with peptides/GAD axon s prouting found six comparisons that correlated sprouting with hilar an d CA4 neuron losses, and four comparisons showing greater sprouting in HS compared to mass lesion/idiopathic. These data indicate that there were greater hilar and CA4 neuron losses and IR axon sprouting for NP Y, SS, and GAD in the epileptogenic human fascia dentata compared to m ass lesion/idiopathic patients with extrahippocampal seizures, and aut opsies. Further, measures of IR sprouting correlated with hilar neuron losses, and hilar and CA4 neuron losses along with peptides/GAD axon sprouting were associated with clinical histories of initial precipita ting injuries to the brain. This supports the notion that in HS reorga nized NPY, SS, and GAD axon circuits, which are possibly inhibitory, m ay reinnervate the dendrites of granule cells following hippocampal in jury and hyperinnervate the proximal dendritic zone, contributing to t he pathophysiology of human hippocampal seizures.