FIG. 6.

Lack of axonal pathology in the hippocampus despite functional alterations. At 7 days after injury or sham conditions, axonal degeneration was assessed both within hippocampal pathways, as well outside the hippocampal structure in sub-cortical white matter tracts (as an internal positive control). Representative micrographs from sham animals are presented in the left column, and from injured animals in the right column. (A, B) In sub-cortical white matter, amyloid precursor protein (APP) immunoreactive axons displayed the classic morphological appearance of traumatic axonal injury, including terminally disconnected swollen axonal bulbs, following TBI (A) but were absent in sham animals (B). However, no overt APP accumulation was observed within the hippocampal formation in any animals following injury, including regions that corresponded to the stimulation/recording sites on the contralateral side (i.e., the stratum moleculare layer of the dentate gyrus and the stratum radiatum of the CA1 region) as demonstrated in representative hippocampal sub-fields following sham conditions (C, E) or head rotation (D, F). Moreover, neurofilament-200 immunolabeling revealed axons of normal density, morphology and distribution in these regions, with consistent appearance between sham (G, I) and injured (H, J) animals. Collectively, these observations suggest the functional compromise of intra-hippocampal axons may not be explained by overt axonal loss/degeneration or transport disruption. Scale bar = 25 μM for (A) and (B), 50 μM for (C-J).