Newseater - Adult Edition

Brain Res, Vol. 535, No. 2. (10 December 1990), pp. 195-204.

The distribution of granule cells in the dentate gyrus of the hippocampal formation was studied in control autopsy and temporal lobe epilepsy (TLE) specimens. In control tissue, the granule cell somata were closely approximated and formed a narrow lamina with a distinct, regular border with the molecular layer. In 11 of 15 TLE specimens, the granule cell somata were dispersed and formed a wider than normal granule cell layer. The granule cell somata extended into the molecular layer to varying extents, creating an irregular boundary between the lamina. The dispersed granule cells were frequently aligned in columns, and many of these neurons displayed elongated bipolar forms. The extent of granule cell dispersion appeared to be related to the amount of cell loss in the polymorph layer of the dentate gyrus. Granule cell dispersion was not consistently associated with granule cell loss although 5 of the 11 specimens with granule cell dispersion also showed moderate to marked granule cell loss. The most common features in the histories of the TLE cases with granule cell dispersion were severe febrile seizures or seizures associated with meningitis or encephalitis during the first 4 years of life. The dispersion of the granule cells suggests that there has been some alteration in the patterns of cell migration in a subpopulation of cases with severe TLE. The resultant ectopic positions of the granule cells could lead to changes in both the afferent and efferent connections of these neurons and, thus, contribute to the altered circuitry of the hippocampal formation in TLE.

Original post by CR Houser

J Neurosci, Vol. 22, No. 14. (15 July 2002), pp. 5797-5802.

The reelin signaling pathway plays a crucial role during the development of laminated structures in the mammalian brain. Reelin, which is synthesized and secreted by Cajal-Retzius cells in the marginal zone of the neocortex and hippocampus, is proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin mRNA by hippocampal Cajal-Retzius cells correlates with the extent of migration defects in the dentate gyrus of patients with temporal lobe epilepsy. These results suggest that reelin is required for normal neuronal lamination in humans, and that deficient reelin expression may be involved in migration defects associated with temporal lobe epilepsy.

Original post by CA Haas

J Neuropathol Exp Neurol, Vol. 64, No. 3. (March 2005), pp. 194-201.

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.

Original post by M Thom