Fig. 4.

Status epilepticus leads to a disruption of normal patterns of newly born granule cell axon outgrowth. A, C, Timm staining of sections from the mid-portion of the hippocampus. Pilocarpine-treated rats demonstrated dense, aberrant reorganization of granule cell mossy fiber terminals into the stratum oriens of the CA3 pyramidal cell region in pilocarpine-treated rats (asterisk in C). This was not typically seen in controls (A), except for occasional mild-to-moderate staining in anterior hippocampal regions. TOAD-64 immunolabeling of similar hippocampal regions in the same control (B) and pilocarpine-treated (D) animals confirmed that the sprouting involved the outgrowth of TOAD-64-immunostained mossy fibers derived from newly postmitotic dentate granule cells (asterisk in D).E, Evidence for the presence of aberrant axons from newly born granule cells in the inner molecular layer of pilocarpine-treated animals. Within the molecular layer, TOAD-IR fibers were seen oriented perpendicular to the normal dendritic pattern of staining (arrowheads). The coexistence of immunoreactive dendrites prohibited the identification of these perpendicular processes as axons. F, G, Double-label immunohistochemistry using antibodies to BrdU and NF-M provided direct evidence for newborn cells sending aberrant axons into the molecular layer. Yellow arrowheads denote BrdU-labeled nuclei of the cells of origin; black arrowheads delineate the trajectory of the NF-M-stained axons. Note the presence of an axonal branch oriented toward the hilus (arrow, G). Scale bar:A–D, 100 μm; E, 50 μm; F, G, 25 μm. dgc, Dentate granule cell layer;h, hilus; m, molecular layer.