Cell proliferation and granule cell dispersion in human hippocampal sclerosis.
Granule cell dispersion (GCD) is observed in approximately 40% of cases of hippocampal sclerosis (HS) in patients with epilepsy. Studies in animal models suggest that GCD may be a consequence of enhanced proliferation of granule cell precursors as a result of seizures. We quantified the number of cells in cycle in subfields of the hippocampus with immunohistochemistry for Mcm2 in 14 HS cases with or without severe GCD compared to 6 epilepsy patients without classical HS or GCD as well as 5 postmortem controls. Higher numbers of Mcm2-positive cells were seen in the region of the granule cell layer in patients with severe GCD, and immunolabeling with Geminin and Ki-67 confirmed a proportion were progressing through cycle. Double labeling with Mcm2 and GFAP confirmed the majority of these cycling cells were GFAP-negative and occasional cells stained colocalized with stem cell marker nestin. These findings support the view that GCD may be a phenomenon related to increased progenitor cell proliferation in patients with hippocampal damage and chronic epilepsy.
Thom
Maria
M
Department of Clinical and Experimental Epilepsy, Institute of Neurology, London, UK. M.Thom@ion.ucl.ac.uk
Martinian
Lillian
L
Williams
Gareth
G
Stoeber
Kai
K
Sisodiya
Sanjay M
SM
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D004827:Epilepsy / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D012598:Sclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018797:Cell Cycle Proteins; D005904:Glial Fibrillary Acidic Protein; D017874:Immediate-Early Proteins; D007211:Indoles; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D064111:Minichromosome Maintenance Complex Component 2; D020559:Monomeric GTP-Binding Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D009687:Nuclear Proteins; D009418:S100 Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C577484:NES protein, human; C007293:DAPI; C084859:MCM2 protein, human; C490245:GEM protein, human