lucifer-yellow and Epilepsy--Temporal-Lobe

Hippocampal dentate granule cells in temporal lobe epilepsy (TLE) patients with mesial sclerosis (MTLE) are reported to be hyperexcitable compared to those in patients with a mass lesion outside the hippocampus (MaTLE) (Williamson, Clin Neurosci 1994;2: 47-52). To determine if such hyperexcitability is associated with an altered morphology of these neurons, Lucifer Yellow-filled granule cells from MTLE patients were compared with those from MaTLE. The morphology of granule cells in both subject groups resembles closely that of human granule cells described previously by Golgi studies. About 40% of human granule cells have basal dendrites. Additionally their apical dendrites are much more limited in their spread in the longitudinal axis of the hippocampus contributing perhaps to a much more narrow lamellar organization than in rats. Analysis of variance computed on 21 morphometric parameters reveals a significant increase in the length of the portion of the dendrite in the inner molecular layer (IML), and a decrease in length in the outer third of the molecular layer in MTLE, compared to MaTLE. Factor analysis performed on the morphometric features of each group of neurons reveals that in the MaTLE neurons the most distinctive feature is the total dendritic length and the overall distribution of spines on them, whereas in MTLE a lengthening and elaboration of the dendrites in the IML is most distinctive. Previous observations of increased synaptic terminals containing neuropeptides, and neurotransmitter receptors in the IML taken in conjunction with an elaboration of granule cell dendrites in this region, suggest considerable synaptic reorganization within the IML of the MTLE hippocampus which may contribute to its epileptogenicity.

Topics: Dendrites; Dentate Gyrus; Epilepsy; Epilepsy, Temporal Lobe; Fluorescent Dyes; Hippocampus; Humans; Isoquinolines; Neuronal Plasticity; Neurons; Sclerosis

Previous histological and immunocytochemical studies suggest that reorganization of the dentate granule cell axons, the mossy fibers, can occur in epileptic human hippocampus (Sutula et al., 1989; Houser et al., 1990; Babb et al., 1991) and in animal models of epilepsy (Tauck and Nadler, 1985; Sutula et al., 1988; Cronin et al., 1992). However, neuroanatomical analyses of the trajectory and morphology of reorganized axons are not yet available. The present study was conducted to investigate single dentate granule cell axonal systems in human epileptic hippocampus. Individual mossy fibers were directly visualized by injecting a tracer (biocytin or Lucifer yellow) intracellularly in hippocampal slices prepared from temporal lobes that were surgically removed from patients for treatment of intractable epilepsy. Two major arborization patterns were identified: (1) the parent axons extended to and coursed through the hilus toward CA3, leaving collaterals along their paths in the hilus (N = 19 neurons); (2) in addition to the aforementioned axonal system, collateral(s) branched from the parent axon near the soma and projected to the granule cell layer and molecular layer, forming an aberrant axonal pathway (N = 9 neurons). These aberrant collaterals bore large boutons similar to those of the hilar axons and formed extensive plexuses in the granule cell layer and/or in the molecular layer. The summed length of collaterals in the granular/molecular layers was 1110.8 microns on average, which was one-fourth of the total summed length of the mossy fibers (3698.5 microns on average). The size of the somata in neurons that had aberrant collaterals was significantly larger than that of neurons without such collaterals (p < 0.025). In four cases, filopodium-like fine processes were present near the axon hillock and proximal parts of the parent axon, suggesting that the aberrant collateral formation might be an ongoing process in these tissues. The lack of control slices from normal living human hippocampus makes it difficult to assess to what extent the present findings are epilepsy associated. However, the presence of aberrant mossy fiber collaterals in the hippocampi used in the present study has been confirmed by Timm's staining and/or dynorphin immunohistochemistry in comparison with nonepileptic autopsy material, indicating its relation to epilepsy (Babb et al., 1991, 1992). At present, there seems to be a consensus that the projection of mossy fiber collaterals t

Topics: Animals; Axons; Biotin; Epilepsy, Temporal Lobe; Fluorescent Dyes; Granulocytes; Hippocampus; Humans; Isoquinolines; Male; Nerve Fibers; Rats